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Sample records for 2-encoded type iii

  1. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Xu, Xuefang; McAteer, Sean P; Tree, Jai J; Shaw, Darren J; Wolfson, Eliza B K; Beatson, Scott A; Roe, Andrew J; Allison, Lesley J; Chase-Topping, Margo E; Mahajan, Arvind; Tozzoli, Rosangela; Woolhouse, Mark E J; Morabito, Stefano; Gally, David L

    2012-01-01

    Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins.

  2. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Xuefang Xu

    Full Text Available Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S system, the production of Shiga toxins (Stx and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90% of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%. PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler. The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins.

  3. Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane.

    Science.gov (United States)

    Gallois, A; Klein, J R; Allen, L A; Jones, B D; Nauseef, W M

    2001-05-01

    Salmonella typhimurium requires a type III secretion system encoded by pathogenicity island (SPI)-2 to survive and proliferate within macrophages. This survival implies that S. typhimurium avoids or withstands bactericidal events targeted to the microbe-containing vacuole, which include intraphagosomal production of reactive oxygen species (ROS), phagosomal acidification, and delivery of hydrolytic enzymes to the phagosome via fusion with lysosomes. Recent evidence suggests that S. typhimurium alters ROS production by murine macrophages in an SPI-2-dependent manner. To gain insights into the mechanism by which S. typhimurium inhibits intraphagosomal ROS production, we analyzed the subcellular distribution of NADPH oxidase components during infection of human monocyte-derived macrophages by wild-type (WT) or several SPI-2 mutant strains of S. typhimurium. We found that the membrane component of the NADPH oxidase, flavocytochrome b(558), was actively excluded or rapidly removed from the phagosomal membrane of WT-infected monocyte-derived macrophages, thereby preventing assembly of the NADPH oxidase complex and intraphagosomal production of superoxide anion. In contrast, the NADPH oxidase assembled on and generated ROS in phagosomes containing SPI-2 mutant S. typhimurium. Subversion of NADPH oxidase assembly by S. typhimurium was accompanied by increased bacterial replication relative to that of SPI-2 mutant strains, suggesting that the ability of WT S. typhimurium to prevent NADPH oxidase assembly at the phagosomal membrane represents an important virulence factor influencing its intracellular survival.

  4. The Salmonella pathogenicity island 2-encoded type III secretion system is essential for the survival of Salmonella enterica serovar Typhimurium in free-living amoebae.

    Science.gov (United States)

    Bleasdale, Benjamin; Lott, Penelope J; Jagannathan, Aparna; Stevens, Mark P; Birtles, Richard J; Wigley, Paul

    2009-03-01

    Free-living amoebae represent a potential reservoir and predator of Salmonella enterica. Through the use of type III secretion system (T3SS) mutants and analysis of transcription of selected T3SS genes, we demonstrated that the Salmonella pathogenicity island 2 is highly induced during S. enterica serovar Typhimurium infection of Acanthamoeba polyphaga and is essential for survival within amoebae.

  5. SseA is a chaperone for the SseB and SseD translocon components of the Salmonella pathogenicity-island-2-encoded type III secretion system.

    Science.gov (United States)

    Ruiz-Albert, Javier; Mundy, Rosanna; Yu, Xiu-Jun; Beuzón, Carmen R; Holden, David W

    2003-05-01

    The type III secretion system (TTSS) encoded by the Salmonella pathogenicity island 2 (SPI-2) is required for bacterial replication inside macrophages and for systemic infection in mice. Many TTSS secreted proteins, including effectors and components of the translocon, require chaperones which promote their stability, prevent their premature interactions or facilitate their secretion. In this study, the function of the first gene (sseA) of one of the SPI-2 operons (sseA-G) was investigated. This operon includes genes that encode translocon components (SseB, SseC and SseD), translocated proteins (SseF and SseG) and putative chaperones (SscA and SscB). sseA encodes a 12.5 kDa protein with a C-terminal region with the potential to form a coiled-coil structure, but no sequence similarity to other proteins. Mutation of sseA results in severe virulence attenuation and an intracellular replication defect. It is shown here that SseA is not a secreted protein, but is required for SPI-2-dependent translocation of two effector proteins (SifA and PipB). Furthermore, the translocon components SseB and SseD were not detected in an sseA mutant strain. By using a yeast two-hybrid assay and column binding experiments, it is demonstrated that SseA interacts directly with SseB and SseD. These results indicate that SseA is a chaperone for SseB and SseD. The inability of an sseA mutant to assemble the SPI-2 TTSS translocon accounts for its high level of virulence attenuation in vivo. To the authors' knowledge, this is the first chaperone described for the SPI-2 TTSS.

  6. The type III manufactory

    CERN Document Server

    Palcoux, Sébastien

    2011-01-01

    Using unusual objects in the theory of von Neumann algebra, as the chinese game Go or the Conway game of life (generalized on finitely presented groups), we are able to build, by hands, many type III factors.

  7. De Novo and Inherited Mutations in COL4A2, Encoding the Type IV Collagen α2 Chain Cause Porencephaly

    Science.gov (United States)

    Yoneda, Yuriko; Haginoya, Kazuhiro; Arai, Hiroshi; Yamaoka, Shigeo; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Yokochi, Kenji; Osaka, Hitoshi; Kato, Mitsuhiro; Matsumoto, Naomichi; Saitsu, Hirotomo

    2012-01-01

    Porencephaly is a neurological disorder characterized by fluid-filled cysts or cavities in the brain that often cause hemiplegia. It has been suggested that porencephalic cavities result from focal cerebral degeneration involving hemorrhages. De novo or inherited heterozygous mutations in COL4A1, which encodes the type IV α1 collagen chain that is essential for structural integrity for vascular basement membranes, have been reported in individuals with porencephaly. Most mutations occurred at conserved Gly residues in the Gly-Xaa-Yaa repeats of the triple-helical domain, leading to alterations of the α1α1α2 heterotrimers. Here we report on two individuals with porencephaly caused by a heterozygous missense mutation in COL4A2, which encodes the type IV α2 collagen chain. Mutations c.3455G>A and c.3110G>A, one in each of the individuals, cause Gly residues in the Gly-Xaa-Yaa repeat to be substituted as p.Gly1152Asp and p.Gly1037Glu, respectively, probably resulting in alterations of the α1α1α2 heterotrimers. The c.3455G>A mutation was found in the proband's mother, who showed very mild monoparesis of the left upper extremity, and the maternal elder uncle, who had congenital hemiplegia. The maternal grandfather harboring the mutation is asymptomatic. The c.3110G>A mutation occurred de novo. Our study confirmed that abnormalities of the α1α1α2 heterotrimers of type IV collagen cause porencephaly and stresses the importance of screening for COL4A2 as well as for COL4A1. PMID:22209246

  8. Coronal type III radio bursts and their X-ray flare and interplanetary type III counterparts

    CERN Document Server

    Reid, Hamish A S

    2016-01-01

    Type III bursts and hard X-rays are both produced by flare energetic electron beams. The link between both emissions has been investigated in many previous studies, but no statistical studies have compared both coronal and interplanetary type III bursts with X-ray flares. Using coronal radio events above 100 MHz exclusively from type III bursts, we revisited long-standing questions: Do all coronal type III bursts have X-ray counterparts. What correlation, if any, occurs between radio and X-ray intensities. What X-ray and radio signatures above 100 MHz occur in connection with interplanetary type III bursts below 14 MHz. We analysed data from 2002 to 2011 starting with coronal type III bursts above 100 MHz. We used RHESSI X-ray data greater than 6 keV to make a list of 321 events that have associated type III bursts and X-ray flares, encompassing at least 28 percent of the initial sample of type III events. We examined the timings, intensities, associated GOES class, and any interplanetary radio signature. For...

  9. Mechanistic insights into type III restriction enzymes.

    Science.gov (United States)

    Raghavendra, Nidhanapati K; Bheemanaik, Shivakumara; Rao, Desirazu N

    2012-01-01

    Type III restriction-modification (R-M) enzymes need to interact with two separate unmethylated DNA sequences in indirectly repeated, head-to-head orientations for efficient cleavage to occur at a defined location next to only one of the two sites. However, cleavage of sites that are not in head-to-head orientation have been observed to occur under certain reaction conditions in vitro. ATP hydrolysis is required for the long-distance communication between the sites prior to cleavage. Type III R-M enzymes comprise two subunits, Res and Mod that form a homodimeric Mod2 and a heterotetrameric Res2Mod2 complex. The Mod subunit in M2 or R2M2 complex recognizes and methylates DNA while the Res subunit in R2M2 complex is responsible for ATP hydrolysis, DNA translocation and cleavage. A vast majority of biochemical studies on Type III R-M enzymes have been undertaken using two closely related enzymes, EcoP1I and EcoP15I. Divergent opinions about how the long-distance interaction between the recognition sites exist and at least three mechanistic models based on 1D- diffusion and/or 3D- DNA looping have been proposed.

  10. NNMSM type-II and -III

    Energy Technology Data Exchange (ETDEWEB)

    Haba, Naoyuki [Graduate School of Science and Engineering, Shimane University, Matsue, Shimane (Japan); Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan); Kaneta, Kunio [Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan); University of Tokyo, Kavli Institute for the Physics and Mathematics of the Universe (WPI), Kashiwa, Chiba (Japan); Osaka University, Department of Physics, Graduate School of Science, Toyonaka, Osaka (Japan); Takahashi, Ryo [Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan)

    2014-01-15

    We suggest two types of extension of the standard model, which are the so-called next to new minimal standard model type-II and -III. They can achieve gauge coupling unification as well as suitable dark matter abundance, small neutrino masses, baryon asymmetry of the universe, inflation, and dark energy. The gauge coupling unification can be realized by introducing two or three extra new fields, and they could explain charge quantization. We also show that there are regions in which the vacuum stability, coupling perturbativity, and correct dark matter abundance can be realized with current experimental data at the same time. (orig.)

  11. Type III Societies (Apparently) Do Not Exist

    CERN Document Server

    Lacki, Brian C

    2016-01-01

    [Abridged] Whether technological societies remain small and planet-bound like our own, or ultimately span across galaxies is an open question in the Search for Extraterrestrial Intelligence. Societies that engineer on a galactic scale are classified as Type III on Kardashev's scale. I argue that Type III societies can take the form of blackboxes, entire galaxies veiled in an opaque screen. A blackbox has a temperature that is just above that of the cosmic microwave background. The screen can be made from artificial dust pervading the galaxy. I show that there is enough material in galaxies to build blackboxes if the dust is fashioned into dipole antennas. The thermal emission of a blackbox makes it a bright microwave source. I examine the Planck Catalog of Compact Sources to constrain the abundance of blackboxes. None of the 100 GHz sources has the spectrum expected of a blackbox. The null result rules out shrouded galaxy clusters out to z ~ 1 and shrouded Milky Ways out to (comoving) 700 Mpc. The reach of th...

  12. Type III apical transportation of root canal

    Directory of Open Access Journals (Sweden)

    Shiv P Mantri

    2012-01-01

    Full Text Available Procedural accidents leading to complications such as canal transportation have been ascribed to inapt cleaning and shaping concepts. Canal transportation is an undesirable deviation from the natural canal path. Herewith a case of apical transportation of root canal resulting in endodontic retreatment failure and its management is presented. A healthy 21-year-old young male presented discomfort and swelling associated with painful endodontically retreated maxillary incisor. Radiograph revealed periradicular radiolucency involving underfilled 11 and overfilled 12. Insufficiently obturated 11 exhibited apical transportation of canal. This type III transportation was treated by periradicular surgery and repair using white mineral trioxide aggregate (MTA. Comfortable asymptomatic patient presented uneventful healing at third and fourth month recall visits. A decrease in the size of radiolucency in radiograph supported the clinical finding. In the present case, MTA is useful in repairing the transportation defect. The result of these procedures is predictable and successful.

  13. Autism Symptoms Related to Tyrosinemia Type III: A Case Report

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    Ayşegül Yolga Tahiroğlu

    2008-08-01

    Full Text Available The published literature on tyrosinemia type III consists of only a few case reports. In this report, we present a patient with tyrosinemia type III, autism, and mental retardation. This patient’s speech improved and his autistic symptoms lessened on a tyrosine-restricted diet, although his mental retardation remained unchanged. This is the first published report of a patient with tyrosinemia type III and autism. This observation is significant due to the paucity of published information about tyrosinemia type III. Turk Jem 2008; 12: 55-6

  14. Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

    Science.gov (United States)

    Odendall, Charlotte; Dixit, Evelyn; Stavru, Fabrizia; Bierne, Helene; Franz, Kate M; Durbin, Ann Fiegen; Boulant, Steeve; Gehrke, Lee; Cossart, Pascale; Kagan, Jonathan C

    2014-08-01

    Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.

  15. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes.

    NARCIS (Netherlands)

    Henneman, P.; Sman-de Beer, F. van der; Moghaddam, P.H.; Huijts, P.; Stalenhoef, A.F.H.; Kastelein, J.J.; Duijn, C.M. van; Havekes, L.M.; Frants, R.R.; Dijk, K.W. van; Smelt, A.H.

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic li

  16. Fine structures of type III radio bursts observed by LOFAR

    Science.gov (United States)

    Magdalenic, Jasmina; Marque, Christophe; Fallows, Richard; Mann, Gottfried; Vocks, Christian

    2017-04-01

    On August 25, 2014, NOAA AR 2146 produced the M2.0 class flare (peaked at 15:11 UT). The flare was associated with a coronal dimming, a EUV wave, a halo CME and a radio event observed by LOFAR (the LOw-Frequency Array). The radio event consisted of a type II, type III and type IV radio emissions. In this study, we focus on LOFAR observations of the type III bursts, generally considered to be radio signatures of fast electron beams propagating along open or quasi open field lines. The group of type III bursts was, as usually, observed during the impulsive phase of the flare. At first hand, type III bursts show no peculiarity, but the high frequency/time resolution LOFAR observations reveal that only few of these type III bursts have a smooth emission profile. The majority of bursts is strongly fragmented. Some show a structuring similar to type IIIb bursts, but on a smaller frequency scale, and others show a non-organized patchy structure which gives indication on the possibly related turbulence processes. Although fine structures of type III bursts were already reported, the wealth of fine structures, and the fragmentation of the radio emission observed in this August 25 event is unprecedented. We show that these LOFAR observations bring completely new insight and pose a new challenge for the physics of the acceleration of electron beams and associated emission processes.

  17. Genetics Home Reference: glycogen storage disease type III

    Science.gov (United States)

    ... Storage Disease (UK) The Association for Glycogen Storage Disease (US) University of Kansas Medical Center Resource List GeneReviews (1 link) Glycogen Storage Disease Type III ClinicalTrials.gov (1 link) ClinicalTrials.gov ...

  18. Guarding the frontiers: the biology of type III interferons

    DEFF Research Database (Denmark)

    Wack, Andreas; Terczynska-Dyla, Ewa; Hartmann, Rune

    2015-01-01

    Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain...

  19. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

    Science.gov (United States)

    Henneman, Peter; van der Sman-de Beer, Femke; Moghaddam, Payman Hanifi; Huijts, Petra; Stalenhoef, Anton FH; Kastelein, John JP; van Duijn, Cornelia M; Havekes, Louis M; Frants, Rune R; van Dijk, Ko Willems; Smelt, Augustinus HM

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (PC polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, PC/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. PMID:19034316

  20. Type III factors with unique Cartan decomposition

    CERN Document Server

    Houdayer, Cyril

    2012-01-01

    We prove that for any free ergodic nonsingular nonamenable action \\Gamma\\ \\actson (X,\\mu) of all \\Gamma\\ in a large class of groups including all hyperbolic groups, the associated group measure space factor $L^\\infty(X) \\rtimes \\Gamma$ has L^\\infty(X) as its unique Cartan subalgebra, up to unitary conjugacy. This generalizes the probability measure preserving case that was established in [PV12]. We also prove primeness and indecomposability results for such crossed products, for the corresponding orbit equivalence relations and for arbitrary amalgamated free products $M_1 *_B M_2$ over a subalgebra B of type I.

  1. Auroral Kilometric Radiation and Type III Solar Radio Bursts

    Science.gov (United States)

    Romantsova, T. V.; Mogilevsky, M. M.; Skalsky, A. A.; Hanasz, J.

    2009-04-01

    Simultaneous wave observations onboard the ISEE-1 and ISEE-3 spacecraft show that onsets of the Auroral Kilometric Radiation frequently coincide with an arrival of type III solar burst (Calvert, 1981). It was supposed that solar burst stimulates maser instability in auroral region and AKR consequently . We present statistical and case studies of events when both type III solar radio bursts and Auroral Kilometric Radiation are recorded simultaneously. AKR was observed onboard the INTERBALL-2 spacecraft orbiting around the Earth by the POLRAD experiment. Wave measurements carried out onboard the Wind, INTEBALL-TAIL and Geotail spacecraft are used to identify unambiguously the type III solar radio bursts. The origin of close relation between onsets of both solar radiation and AKR is discussed and interpreted. Acknowledgements. This work is supported by grant RFBR 06-02-72560.

  2. Assessment of sleep in children with mucopolysaccharidosis type III.

    Directory of Open Access Journals (Sweden)

    Louise Victoria Mahon

    Full Text Available Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III, yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7-10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice.

  3. Exploiting the Biosynthetic Potential of Type III Polyketide Synthases

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    Yan Ping Lim

    2016-06-01

    Full Text Available Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development.

  4. Tyrosinemia Type III detected via neonatal screening: management and outcome.

    Science.gov (United States)

    Heylen, Evelyne; Scherer, Gerd; Vincent, Marie-Françoise; Marie, Sandrine; Fischer, Judith; Nassogne, Marie-Cécile

    2012-11-01

    Tyrosinemia Type III is caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), an enzyme involved in the catabolic pathway of tyrosine. To our knowledge, only a few patients presenting with this disease have been described in the literature, and the clinical phenotype remains variable and unclear. We report the case of a boy with tyrosinemia Type III detected using neonatal screening, who is homozygous for the splice donor mutation IVS11+1G>A in intron 11 of the HPD gene. At the age of 30 months, the boy's outcome under mild protein restriction was characterized by normal growth and psychomotor development.

  5. Type III restriction-modification enzymes: a historical perspective.

    Science.gov (United States)

    Rao, Desirazu N; Dryden, David T F; Bheemanaik, Shivakumara

    2014-01-01

    Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction-modification (R-M) systems are classified into four groups. Type III R-M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25-27 bp downstream of one of the recognition sites). Like the Type I R-M enzymes, Type III R-M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R-M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R-M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.

  6. Type III von Neumann Algebras associated with $\\O_\\theta$

    CERN Document Server

    Yang, Dilian

    2011-01-01

    Let $\\Fth$ be a 2 graph generated by $m$ blue edges and $n$ red edges, and $\\omega$ be the distinguished faithful state associated with its graph C*-algebra $\\O_\\theta$. In this paper, we characterize the factorness of the von Neumann algebra $\\pi_\\omega(\\O_\\theta)"$ induced from the GNS representation of $\\omega$ under a certain condition. Moreover, when $\\pi_\\omega(\\O_\\theta)"$ is a factor, then it is of type III$_{m^{-\\frac{1}{b}}}$ (or III$_{n^{-\\frac{1}{a}}}$) if $\\frac{\\ln m}{\\ln n}\\in\\bQ$, where $a,b\\in\\bN$ with $\\gcd(a,b)=1$ satisfy $m^a=n^b$, and of type III$_1$ if $\\frac{\\ln m}{\\ln n}\

  7. Microwave Type III Pair Bursts in Solar Flares

    CERN Document Server

    Tan, Baolin; Karlicky, Marian; Huang, Guangli; Tan, Chengming

    2016-01-01

    Solar microwave type III pair burst is composed of normal and reverse-sloped (RS) burst branches with oppositely fast frequency drifts. It is the most sensitive signature of the primary energy release and electron accelerations in flares. This work reported 11 microwave type III pair events in 9 flares observed by radio spectrometers in China and the Czech Republic at frequency of 0.80 - 7.60 GHz during 1994 - 2014. These type III pairs occurred in flare impulsive and postflare phases with separate frequency in range of 1.08 - 3.42 GHz and frequency gap 10 - 1700 MHz. The frequency drift increases with the separate frequency (f_{x}), the lifetime of each burst is anti-correlated to f_{x}, while the frequency gap is independent to f_{x}. In most events, the normal branches are drifting obviously faster than the RS branches. The type III pairs occurring in flare impulsive phase have lower separate frequency, longer lifetime, wider frequency gap, and slower frequency drift than that occurring in postflare phase....

  8. Type III effector-mediated processes in Salmonella infection.

    Science.gov (United States)

    van der Heijden, Joris; Finlay, B Brett

    2012-06-01

    Salmonella is one of the most successful bacterial pathogens that infect humans in both developed and developing countries. In order to cause infection, Salmonella uses type III secretion systems to inject bacterial effector proteins into host cells. In the age of antibiotic resistance, researchers have been looking for new strategies to reduce Salmonella infection. To understand infection and to analyze type III secretion as a potential therapeutic target, research has focused on identification of effectors, characterization of effector functions and how they contribute to disease. Many effector-mediated processes have been identified that contribute to infection but thus far no specific treatment has been found. In this perspective we discuss our current understanding of effector-mediated processes and discuss new techniques and approaches that may help us to find a solution to this worldwide problem.

  9. Identification of Novel Type III Effectors Using Latent Dirichlet Allocation

    Directory of Open Access Journals (Sweden)

    Yang Yang

    2012-01-01

    Full Text Available Among the six secretion systems identified in Gram-negative bacteria, the type III secretion system (T3SS plays important roles in the disease development of pathogens. T3SS has attracted a great deal of research interests. However, the secretion mechanism has not been fully understood yet. Especially, the identification of effectors (secreted proteins is an important and challenging task. This paper adopts machine learning methods to identify type III secreted effectors (T3SEs. We extract features from amino acid sequences and conduct feature reduction based on latent semantic information by using latent Dirichlet allocation model. The experimental results on Pseudomonas syringae data set demonstrate the good performance of the new methods.

  10. Evaluation of Salmonella enterica type III secretion system effector proteins as carriers for heterologous vaccine antigens.

    Science.gov (United States)

    Hegazy, Wael Abdel Halim; Xu, Xin; Metelitsa, Leonid; Hensel, Michael

    2012-03-01

    Live attenuated strains of Salmonella enterica have a high potential as carriers of recombinant vaccines. The type III secretion system (T3SS)-dependent translocation of S. enterica can be deployed for delivery of heterologous antigens to antigen-presenting cells. Here we investigated the efficacy of various effector proteins of the Salmonella pathogenicity island (SPI2)-encoded T3SS for the translocation of model antigens and elicitation of immune responses. The SPI2 T3SS effector proteins SifA, SteC, SseL, SseJ, and SseF share an endosomal membrane-associated subcellular localization after translocation. We observed that all effector proteins could be used to translocate fusion proteins with the model antigens ovalbumin and listeriolysin into the cytosol of host cells. Under in vitro conditions, fusion proteins with SseJ and SteC stimulated T-cell responses that were superior to those triggered by fusion proteins with SseF. However, in mice vaccinated with Salmonella carrier strains, only fusion proteins based on SseJ or SifA elicited potent T-cell responses. These data demonstrate that the selection of an optimal SPI2 effector protein for T3SS-mediated translocation is a critical parameter for the rational design of effective Salmonella-based recombinant vaccines.

  11. Tape Casting of Honeywell PZT Type III Powder.

    Science.gov (United States)

    1984-02-01

    STANDARDS 193 A . . . • . .I-" ’ .7. ’. .. ’. .-7 . • " U) 1 IV. Tape Casting of Honeywell PZT Type III Poder II~ II * I S Gordon 0. Dayton Beth A. Jones...Street Port Hueneme, CA 93043 Arlington, VA 22217 3 ATTN: Materials Division Attn: Code 431 Naval Research Laboratory Naval Electronics Laboratory...Washington, DC 20375 San Diego, CA 92152 ATTN: Codes 6000 1 ATTN: Electron Materials 6300 1 Sciences Division 2627 1 Naval Air Development Center Naval

  12. Emission Patterns of Solar Type III Radio Bursts: Stereoscopic Observations

    Science.gov (United States)

    Thejappa, G.; MacDowall, R.; Bergamo, M.

    2012-01-01

    Simultaneous observations of solar type III radio bursts obtained by the STEREO A, B, and WIND spacecraft at low frequencies from different vantage points in the ecliptic plane are used to determine their directivity. The heliolongitudes of the sources of these bursts, estimated at different frequencies by assuming that they are located on the Parker spiral magnetic field lines emerging from the associated active regions into the spherically symmetric solar atmosphere, and the heliolongitudes of the spacecraft are used to estimate the viewing angle, which is the angle between the direction of the magnetic field at the source and the line connecting the source to the spacecraft. The normalized peak intensities at each spacecraft Rj = Ij /[Sigma]Ij (the subscript j corresponds to the spacecraft STEREO A, B, and WIND), which are defined as the directivity factors are determined using the time profiles of the type III bursts. It is shown that the distribution of the viewing angles divides the type III bursts into: (1) bursts emitting into a very narrow cone centered around the tangent to the magnetic field with angular width of approximately 2 deg and (2) bursts emitting into a wider cone with angular width spanning from [approx] -100 deg to approximately 100 deg. The plots of the directivity factors versus the viewing angles of the sources from all three spacecraft indicate that the type III emissions are very intense along the tangent to the spiral magnetic field lines at the source, and steadily fall as the viewing angles increase to higher values. The comparison of these emission patterns with the computed distributions of the ray trajectories indicate that the intense bursts visible in a narrow range of angles around the magnetic field directions probably are emitted in the fundamental mode, whereas the relatively weaker bursts visible to a wide range of angles are probably emitted in the harmonic mode.

  13. On the theory of the type III burst exciter

    Science.gov (United States)

    Smith, R. A.; Goldstein, M. L.; Papadopoulos, K.

    1976-01-01

    In situ satellite observations of type III burst exciters at 1 AU show that the beam does not evolve into a plateau in velocity space, contrary to the prediction of quasilinear theory. The observations can be explained by a theory that includes mode coupling effects due to excitation of the parametric oscillating two-stream instability and its saturation by anomalous resistivity. The time evolution of the beam velocity distribution is included in the analysis.

  14. Emission Patterns of Solar Type III Radio Bursts: Stereoscopic Observations

    Science.gov (United States)

    Thejappa, G.; MacDowall, R.; Bergamo, M.

    2012-01-01

    Simultaneous observations of solar type III radio bursts obtained by the STEREO A, B, and WIND spacecraft at low frequencies from different vantage points in the ecliptic plane are used to determine their directivity. The heliolongitudes of the sources of these bursts, estimated at different frequencies by assuming that they are located on the Parker spiral magnetic field lines emerging from the associated active regions into the spherically symmetric solar atmosphere, and the heliolongitudes of the spacecraft are used to estimate the viewing angle, which is the angle between the direction of the magnetic field at the source and the line connecting the source to the spacecraft. The normalized peak intensities at each spacecraft Rj = Ij /[Sigma]Ij (the subscript j corresponds to the spacecraft STEREO A, B, and WIND), which are defined as the directivity factors are determined using the time profiles of the type III bursts. It is shown that the distribution of the viewing angles divides the type III bursts into: (1) bursts emitting into a very narrow cone centered around the tangent to the magnetic field with angular width of approximately 2 deg and (2) bursts emitting into a wider cone with angular width spanning from [approx] -100 deg to approximately 100 deg. The plots of the directivity factors versus the viewing angles of the sources from all three spacecraft indicate that the type III emissions are very intense along the tangent to the spiral magnetic field lines at the source, and steadily fall as the viewing angles increase to higher values. The comparison of these emission patterns with the computed distributions of the ray trajectories indicate that the intense bursts visible in a narrow range of angles around the magnetic field directions probably are emitted in the fundamental mode, whereas the relatively weaker bursts visible to a wide range of angles are probably emitted in the harmonic mode.

  15. Fuel of the Bacterial Flagellar Type III Protein Export Apparatus.

    Science.gov (United States)

    Minamino, Tohru; Kinoshita, Miki; Namba, Keiichi

    2017-01-01

    The flagellar type III export apparatus utilizes ATP and proton motive force (PMF) across the cytoplasmic membrane as the energy sources and transports flagellar component proteins from the cytoplasm to the distal growing end of the growing structure to construct the bacterial flagellum beyond the cellular membranes. The flagellar type III export apparatus coordinates flagellar protein export with assembly by ordered export of substrates to parallel with their order of the assembly. The export apparatus is composed of a PMF-driven transmembrane export gate complex and a cytoplasmic ATPase complex. Since the ATPase complex is dispensable for flagellar protein export, PMF is the primary fuel for protein unfolding and translocation. Interestingly, the export gate complex can also use sodium motive force across the cytoplasmic membrane in addition to PMF when the ATPase complex does not work properly. Here, we describe experimental protocols, which have allowed us to identify the export substrate class and the primary fuel of the flagellar type III protein export apparatus in Salmonella enterica serovar Typhimurium.

  16. Assembly of the bacterial type III secretion machinery.

    Science.gov (United States)

    Diepold, Andreas; Wagner, Samuel

    2014-07-01

    Many bacteria that live in contact with eukaryotic hosts, whether as symbionts or as pathogens, have evolved mechanisms that manipulate host cell behaviour to their benefit. One such mechanism, the type III secretion system, is employed by Gram-negative bacterial species to inject effector proteins into host cells. This function is reflected by the overall shape of the machinery, which resembles a molecular syringe. Despite the simplicity of the concept, the type III secretion system is one of the most complex known bacterial nanomachines, incorporating one to more than hundred copies of up to twenty different proteins into a multi-MDa transmembrane complex. The structural core of the system is the so-called needle complex that spans the bacterial cell envelope as a tripartite ring system and culminates in a needle protruding from the bacterial cell surface. Substrate targeting and translocation are accomplished by an export machinery consisting of various inner membrane embedded and cytoplasmic components. The formation of such a multimembrane-spanning machinery is an intricate task that requires precise orchestration. This review gives an overview of recent findings on the assembly of type III secretion machines, discusses quality control and recycling of the system and proposes an integrated assembly model.

  17. Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator.

    Science.gov (United States)

    Imada, Katsumi; Minamino, Tohru; Uchida, Yumiko; Kinoshita, Miki; Namba, Keiichi

    2016-03-29

    FliI and FliJ form the FliI6FliJ ATPase complex of the bacterial flagellar export apparatus, a member of the type III secretion system. The FliI6FliJ complex is structurally similar to the α3β3γ complex of F1-ATPase. The FliH homodimer binds to FliI to connect the ATPase complex to the flagellar base, but the details are unknown. Here we report the structure of the homodimer of a C-terminal fragment of FliH (FliHC2) in complex with FliI. FliHC2 shows an unusually asymmetric homodimeric structure that markedly resembles the peripheral stalk of the A/V-type ATPases. The FliHC2-FliI hexamer model reveals that the C-terminal domains of the FliI ATPase face the cell membrane in a way similar to the F/A/V-type ATPases. We discuss the mechanism of flagellar ATPase complex formation and a common origin shared by the type III secretion system and the F/A/V-type ATPases.

  18. Nonlinear Spinor Fields in Bianchi type-III spacetime

    CERN Document Server

    Saha, Bijan

    2016-01-01

    Within the scope of Bianchi type-III spacetime we study the role of spinor field on the evolution of the Universe as well as the influence of gravity on the spinor field. In doing so we have considered a polynomial type of nonlinearity. In this case the spacetime remains locally rotationally symmetric and anisotropic all the time. It is found that depending on the sign of nonlinearity the models allows both accelerated and oscillatory modes of expansion. The non-diagonal components of energy-momentum tensor though impose some restrictions on metric functions and components of spinor field, unlike Bianchi type I, V and $VI_0$ cases, they do not lead to vanishing mass and nonlinear terms of the spinor field.

  19. $\\ell_1 \\to \\ell_2 \\gamma$ in type III seesaw

    CERN Document Server

    Bonnet, F

    2008-01-01

    We study the decay rates of the $\\mu \\to e \\gamma$ and $\\tau \\to \\ell \\gamma$ transitions in the framework of the type III seesaw model, where fermionic triplets are exchanged to generate neutrino masses. We show that the observation of one of those decays in planned experiments would contradict bounds arising from present experimental limits on the $\\mu \\to eee$ and $\\tau \\to 3 l$ decay rates, and therefore imply that there exist other sources of lepton flavour violation than those associated to triplet of fermions.

  20. Guadalajara camptodactyly type III: a new probably autosomal dominant syndrome.

    Science.gov (United States)

    Figuera, L E; Ramírez-Dueñas, M L; Dávalos, I P; Cantú, J M

    2002-10-01

    A Mexican family is presented with the main clinical features of camptodactyly, a distinctive facial appearance because of ocular hypertelorism, telecanthus, symblepharon and spinal defects. Other clinical manifestations included: multiple nevi, simplified ears, retrognathia, congenital shortness of the sternocleidomastoid muscle, thin hands and feet, a small penis and mild mental retardation. Radiographic studies revealed spina bifida occulta at cervical and dorso-lumbar levels, increased bone trabeculae, cortical thickening and delayed bone age. The presence of five affected members through four generations suggests autosomal dominant inheritance although no male-to-male transmission was documented. The authors propose this as a new entity, and have designated it Guadalajara camptodactyly type III.

  1. Numerical simulations of type III planetary migration: III. Outward migration of massive planets

    CERN Document Server

    Peplinski, A; Mellema, G

    2008-01-01

    We present a numerical study of rapid, so called type III migration for Jupiter-sized planets embedded in a protoplanetary disc. We limit ourselves to the case of outward migration, and study in detail its evolution and physics, concentrating on the structure of the co-rotation and circumplanetary regions, and processes for stopping migration. We also consider the dependence of the migration behaviour on several key parameters. We perform this study using global, two-dimensional hydrodynamical simulations with adaptive mesh refinement. We find that the outward directed type III migration can be started if the initial conditions support $Z > 1$, that corresponds to initial value $M_\\rmn{\\Delta} \\ga 1.5$. Unlike the inward directed migration, in the outward migration the migration rate increases due to the growing of the volume of the co-orbital region. We find the migration to be strongly dependent on the rate of the mass accumulation in the circumplanetary disc, leading to two possible regimes of migration, f...

  2. A Probable Short Decimetric Type I-like Noise Storm: Associated with Type III Bursts?

    Institute of Scientific and Technical Information of China (English)

    Rui-Xiang Xie; Min Wang; Yi-Hua Yan

    2005-01-01

    A rare Type I-like noise storm was observed with the solar radio spectrometers (1.0-2.0 GHz and 2.60-3.8 GHz) at National Astronomical Observatories of China (NAOC) on September 23, 1998. We concentrate on checking the Type I-like noise storm occurred in the decay phase of a Type IV radio burst. This noise storm consists of many Type I bursts and isolated Type III or Type III pair bursts.It has a bandwidth of ≤ 0.5 GHz. The duration of each Type I burst is of the order of 100-300ms. The total duration is greater than 11 minutes. The circular polarization degree of the components of Type I and associated Type III bursts are about 40%-100% and almost 100%, respectively, which is greater than that of the background continuum (nearly the precision of our instrument). This short decimetric Type I-like storm may be another kind or the extension of the kind of metric Type I storm, and may possess the duality of metric and decimetric radio emission. It may be in favor of an earlier emission mechanism of the fundamental plasma radiation due to the coalescence of Langmuir waves with low-frequency waves.

  3. Outcome of Gartland type II and type III supracondylar fractures treated by Blount′s technique

    Directory of Open Access Journals (Sweden)

    de Gheldere Antoine

    2010-01-01

    Full Text Available Background : According to some orthopedic surgeons, almost all supracondylar humerus fractures should be treated operatively by reduction and pinning. While according to others, closed reduction and immobolization should be used for Gartland type II and some type III fractures. However, the limit of this technique remains unclear. We present 74 patients with displaced extension-type supracondylar fractures treated by closed reduction and immobilization with a collar sling fixed to a cast around the wrist. The purpose of the study is to give a more precise limitation of this technique. Materials and Methods : Retrospective data acquisition of 74 patients with a Gartland type II or type III fractures treated by closed reduction and immobilization (Blount′s technique between January 2004 and December 2007 was done. The mean age was 6.3 years (range, 2-11. The mean time of follow-up was 6.5 months (range, 3-25. All open injuries and complex elbow fracture dislocations or T-condylar fractures were excluded from the study. All patients were evaluated with standardized anteroposterior and true lateral x-rays of the elbow, and Flynn criteria were used for functional assessment. Results : Gartland type II fractures had 94% good or excellent final results. Gartland type III fractures had 73% good or excellent final result. The Gartland type III outcome depended on the displacement. The fractures remained stable in 88% for the posterior displacement, and 58% for the posteromedial displacement. These displacements were mild. However, for the posterolaterally displaced fractures, only 36% were stable; 36% had a mild displacement and 27% had a major displacement. Conclusion : Pure posterior displacement is more stable than posteromedial displacement which is more stable than posterolaterally displaced fractures. This study suggests that Gartland type II and pure posterior or posteromedial displaced Gartland type III fractures can be treated by closed

  4. A Novel Type III Endosome Transmembrane Protein, TEMP

    Directory of Open Access Journals (Sweden)

    Rohan D. Teasdale

    2012-11-01

    Full Text Available As part of a high-throughput subcellular localisation project, the protein encoded by the RIKEN mouse cDNA 2610528J11 was expressed and identified to be associated with both endosomes and the plasma membrane. Based on this, we have assigned the name TEMP for Type III Endosome Membrane Protein. TEMP encodes a short protein of 111 amino acids with a single, alpha-helical transmembrane domain. Experimental analysis of its membrane topology demonstrated it is a Type III membrane protein with the amino-terminus in the lumenal, or extracellular region, and the carboxy-terminus in the cytoplasm. In addition to the plasma membrane TEMP was localized to Rab5 positive early endosomes, Rab5/Rab11 positive recycling endosomes but not Rab7 positive late endosomes. Video microscopy in living cells confirmed TEMP's plasma membrane localization and identified the intracellular endosome compartments to be tubulovesicular. Overexpression of TEMP resulted in the early/recycling endosomes clustering at the cell periphery that was dependent on the presence of intact microtubules. The cellular function of TEMP cannot be inferred based on bioinformatics comparison, but its cellular distribution between early/recycling endosomes and the plasma membrane suggests a role in membrane transport.

  5. Biphenyl synthase, a novel type III polyketide synthase.

    Science.gov (United States)

    Liu, B; Raeth, T; Beuerle, T; Beerhues, L

    2007-05-01

    Biphenyls and dibenzofurans are the phytoalexins of the Maloideae, a subfamily of the economically important Rosaceae. The carbon skeleton of the two classes of antimicrobial secondary metabolites is formed by biphenyl synthase (BIS). A cDNA encoding this key enzyme was cloned from yeast-extract-treated cell cultures of Sorbus aucuparia. BIS is a novel type III polyketide synthase (PKS) that shares about 60% amino acid sequence identity with other members of the enzyme superfamily. Its preferred starter substrate is benzoyl-CoA that undergoes iterative condensation with three molecules of malonyl-CoA to give 3,5-dihydroxybiphenyl via intramolecular aldol condensation. BIS did not accept CoA-linked cinnamic acids such as 4-coumaroyl-CoA. This substrate, however, was the preferential starter molecule for chalcone synthase (CHS) that was also cloned from S. aucuparia cell cultures. While BIS expression was rapidly, strongly and transiently induced by yeast extract treatment, CHS expression was not. In a phylogenetic tree, BIS grouped together closely with benzophenone synthase (BPS) that also uses benzoyl-CoA as starter molecule but cyclizes the common intermediate via intramolecular Claisen condensation. The molecular characterization of BIS thus contributes to the understanding of the functional diversity and evolution of type III PKSs.

  6. 77 FR 76426 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Science.gov (United States)

    2012-12-28

    ... organizations that are not functionally integrated. The withdrawal affects Type III supporting organizations... ``Type III Supporting Organizations''). Those regulations reflect changes to the law made by the Pension... Revenue Service 26 CFR Part 1 [REG 155929-06] RIN 1545-BL44 Payout Requirements for Type III...

  7. Hereditary sensory and autonomic neuropathies: types II, III, and IV.

    Science.gov (United States)

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-10-03

    The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  8. Hereditary sensory and autonomic neuropathies: types II, III, and IV

    Directory of Open Access Journals (Sweden)

    Axelrod Felicia B

    2007-10-01

    Full Text Available Abstract The hereditary sensory and autonomic neuropathies (HSAN encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating. Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III, which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  9. Elective visceral hybrid repair of type III thoracoabdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2012-01-01

    Full Text Available Introduction. According to the classification given by Crawford et al. type III thoracoabdominal aortic aneurysm (TAAA is dilatation of the aorta from the level of the rib 6 to the separation of the aorta below the renal arteries, capturing all the visceral branch of aorta. Visceral hybrid reconstruction of TAAA is a procedure developed in recent years in the world, which involves a combination of conventional, open and endovascular aortic reconstruction surgery at the level of separation of the left subclavian artery to the level of visceral branches of aorta. Case report. We presented a 75-years-old man, with elective visceral hybrid reconstruction of type III TAAA. Computerized scanning (CT angiography of the patient showed type III TAAA with the maximum transverse diameter of aneurysm of 92 mm. Aneurysm started at the level of the sixth rib, and the end of the aneurysm was 1 cm distal to the level of renal arteries. Aneurysm compressed the esophagus, causing the patient difficulty in swallowing act, especially solid food, and frequent back pain. From the other comorbidity, the patient had been treated for a long time, due to chronic obstructive pulmonary disease and hypertension. In general endotracheal anesthesia with epidural analgesia, the patient underwent visceral hybrid reconstruction of TAAA, which combines classic, open vascular surgery and endovascular procedures. Classic vascular surgery is visceral reconstruction using by-pass procedure from the distal, normal aorta to all visceral branches: celiac trunk, superior mesenteric artery and both renal arteries, with ligature of all arteries very close to the aorta. After that, by synchronous endovascular technique a complete aneurysmal exclusion of thoracoabdominal aneurysm with thoracic stent-graft was performed. The postoperative course was conducted properly and the patient left the Clinic for Vascular Surgery on postoperative day 21. Control CT, performed 3 months after the surgery

  10. Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL.

    Science.gov (United States)

    Coombes, Brian K; Brown, Nat F; Valdez, Yanet; Brumell, John H; Finlay, B Brett

    2004-11-26

    Salmonella pathogenicity island (SPI)-2 is pivotal to the intracellular survival of Salmonella and for virulence in mammals. SPI-2 encodes virulence factors (called effectors) that are translocated into the host cell, a type III secretion apparatus and a two-component regulatory system that regulates intracellular expression of SPI-2. Salmonella SPI-2 secretion activity appears to be induced in response to acidification of the vacuole in which it replicates. Here we show that the expression of the SPI-2 proteins, SseB and SseD (filament and pore forming components of the secretion apparatus, respectively) in response to acidification requires an intact secretion system and SsaL, a Salmonella homologue of SepL, a regulator required for type III-dependent secretion of translocators but not effectors in attaching and effacing gastrointestinal pathogens. We show that the expression of SPI-2-encoded effectors is acid-regulated but can be uncoupled from the expression of filament and translocon components, thus showing a differential requirement of SsaL for expression. The secretion and translocation of SPI-2-encoded effectors requires SsaL, but SsaL is dispensable for the secretion of SPI-2 effectors encoded in other pathogenicity loci, suggesting a secretion regulation function for SsaL. Further, we demonstrate that the differential expression of adjacent genes within the sseA operon (sseD and sseE) occurs at the transcriptional level. These data indicate that a Salmonella SPI-2 activation state is achieved by an acidregulated response that requires SsaL. These data also suggest the existence of a previously unrecognized regulatory element within SPI-2 for the "effector operon" region downstream of sseD that might demarcate the expression of translocators and effectors.

  11. The Structure and Function of Type III Secretion Systems.

    Science.gov (United States)

    Notti, Ryan Q; Stebbins, C Erec

    2016-02-01

    Type III secretion systems (T3SSs) afford Gram-negative bacteria an intimate means of altering the biology of their eukaryotic hosts--the direct delivery of effector proteins from the bacterial cytoplasm to that of the eukaryote. This incredible biophysical feat is accomplished by nanosyringe "injectisomes," which form a conduit across the three plasma membranes, peptidoglycan layer, and extracellular space that form a barrier to the direct delivery of proteins from bacterium to host. The focus of this chapter is T3SS function at the structural level; we will summarize the core findings that have shaped our understanding of the structure and function of these systems and highlight recent developments in the field. In turn, we describe the T3SS secretory apparatus, consider its engagement with secretion substrates, and discuss the posttranslational regulation of secretory function. Lastly, we close with a discussion of the future prospects for the interrogation of structure-function relationships in the T3SS.

  12. Type III secretion systems shape up as they ship out.

    Science.gov (United States)

    Marlovits, Thomas C; Stebbins, C Erec

    2010-02-01

    Virulence associated protein type III secretion systems (T3SSs) are intricately structured organic nanosyringes that achieve the translocation of bacterial proteins from the prokaryotic cytoplasm across three membranes into the host cytosol. The substrates for these systems number in the hundreds, with remarkably diverse biological activities, modulating host cell biology for the benefit of the pathogen. Although there has been tremendous progress on the structure and function of the T3SS substrates, there has been comparatively little progress on the much more highly conserved secretion apparatus itself. This review summarizes recent advances in the field of structural microbiology that have begun to address this shortcoming, finally bringing to bear the power of structural biology to this central virulence system of Gram-negative bacterial pathogens. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. Prevalence of type III secretion system in effective biocontrol pseudomonads.

    Science.gov (United States)

    Almario, Juliana; Gobbin, Davide; Défago, Geneviève; Moënne-Loccoz, Yvan; Rezzonico, Fabio

    2014-05-01

    Functional type III secretion system (T3SS) genes are needed for effective biocontrol of Pythium damping-off of cucumber by Pseudomonas fluorescens KD, but whether biocontrol Pseudomonas strains with T3SS genes display overall a higher plant-protecting activity is unknown. The assessment of 198 biocontrol fluorescent pseudomonads originating from 60 soils worldwide indicated that 32% harbour the ATPase-encoding T3SS gene hrcN, which was most often found in tomato isolates. The hrcN(+) biocontrol strains (and especially those also producing 2,4-diacetylphloroglucinol and displaying 1-aminocyclopropane-1-carboxylate deaminase activity) displayed higher plant-protecting ability in comparison with hrcN(-) biocontrol strains, both in the Pythium/cucumber and Fusarium/cucumber pathosystems.

  14. Yersinia Type III Secretion System Master Regulator LcrF

    Science.gov (United States)

    Schwiesow, Leah; Lam, Hanh

    2015-01-01

    Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters. PMID:26644429

  15. High-Frequency Cutoff in Type III Bursts

    Science.gov (United States)

    Stanislavsky, A. A.; Konovalenko, A. A.; Volvach, Ya. S.; Koval, A. A.

    In this article we report about a group of solar bursts with high-frequency cutoff, observed on 19 August of 2012 near 8:23 UT, simultaneously by three different radio telescopes: the Ukrainian decameter radio telescope (8-33 MHz), the French Nancay Decametric Array (10-70 MHz) and the Italian San Vito Solar Observatory of RSTN (25-180 MHz). Morphologically the bursts are very similar to the type III bursts. The solar activity is connected with the emergency of a new group of solar spots on the far side of the Sun with respect to observers on Earth. The solar bursts accompany many moderate flares over eastern limb. The refraction of the behind-limb radio bursts towards the Earth is favorable, if CMEs generate low-density cavities in solar corona.

  16. Yersinia Type III Secretion System Master Regulator LcrF.

    Science.gov (United States)

    Schwiesow, Leah; Lam, Hanh; Dersch, Petra; Auerbuch, Victoria

    2015-12-07

    Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters.

  17. Harnessing type I and type III CRISPR-Cas systems for genome editing

    DEFF Research Database (Denmark)

    Li, Yingjun; Pan, Saifu; Zhang, Yan

    2016-01-01

    report on harnessing a Type I or Type III system for genome editing. Here, a method was developed to repurpose both CRISPR-Cas systems for genetic manipulation in Sulfolobus islandicus, a thermophilic archaeon. A novel type of genome-editing plasmid (pGE) was constructed, carrying an artificial mini......CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are widespread in archaea and bacteria, and research on their molecular mechanisms has led to the development of genome-editing techniques based on a few Type II systems. However, there has not been any...

  18. Harnessing type I and type III CRISPR-Cas systems for genome editing

    DEFF Research Database (Denmark)

    Li, Yingjun; Pan, Saifu; Zhang, Yan;

    2016-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are widespread in archaea and bacteria, and research on their molecular mechanisms has led to the development of genome-editing techniques based on a few Type II systems. However, there has not been any...... report on harnessing a Type I or Type III system for genome editing. Here, a method was developed to repurpose both CRISPR-Cas systems for genetic manipulation in Sulfolobus islandicus, a thermophilic archaeon. A novel type of genome-editing plasmid (pGE) was constructed, carrying an artificial mini...

  19. Type II and Type III Radio Bursts and their Correlation with Solar Energetic Proton Events

    CERN Document Server

    Winter, L M

    2015-01-01

    Using the Wind/WAVES radio observations from 2010-2013, we present an analysis of the 123 decametric-hectometric (DH) type II solar radio bursts during this period, the associated type III burst properties, and their correlation with solar energetic proton (SEP) properties determined from analysis of the Geostationary Operational Environmental Satellite (GOES) observations. We present a useful catalog of the type II burst, type III burst, Langmuir wave, and proton flux properties for these 123 events, which we employ to develop a statistical relationship between the radio properties and peak proton flux that can be used to forecast SEP events. We find that all SEP events with a peak > 10 MeV flux above 15 pfu are associated with a type II burst and virtually all SEP events, 92%, are also associated with a type III radio burst. Based on a principal component analysis, the radio burst properties that are most highly correlated with the occurrence of gradual SEP events and account for the most variance in the ra...

  20. Hereditary angioedema with normal C1-INH (HAE type III).

    Science.gov (United States)

    Riedl, Marc A

    2013-01-01

    Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency.

  1. Pulmonary involvement in siblings with Gaucher disease type III

    Directory of Open Access Journals (Sweden)

    Đorđević Maja

    2011-01-01

    Full Text Available Introduction. Pulmonary involvement has been described in all types of Gaucher disease (GD but it is considered as relatively rare manifestation. There are reports suggesting that homozygosity for L444P mutation in GBA gene is associated with a substantial risk for developing primary pulmonary disease in GD. Case report. We reported sisters with pulmonary involvement in GD type III. Respiratory failure with fatal outcome at 3 years and 4 months of age occurred in K.K. due to pulmonary complications of GD. At the time enzyme replacement therapy (ERT was not available in Serbia. J.K., homozygous for L444P mutation, developed asymptomatic pulmonary involvement at the age of 6 after 2.5 years of ERT. Pulmonary disease in J.K. was verified by high resolution computerized tomography, cytology of bronchoalveolar lavage fluid and histopathology of transbronchial lung biopsy. Conclusion. Primary lung disease in children homoallelic for L444P mutation in GBA gene emerges as a significant clinical manifestation of GD with unclear response to ERT.

  2. pKBuS13, a KPC-2-Encoding Plasmid from Klebsiella pneumoniae Sequence Type 833, Carrying Tn4401b Inserted into an Xer Site-Specific Recombination Locus

    Science.gov (United States)

    Garbari, Luigi; Busetti, Marina; Dolzani, Lucilla; Petix, Vincenzo; Knezevich, Anna; Bressan, Raffaela; Gionechetti, Fabrizia; Tonin, Enrico A.

    2015-01-01

    Here, we report the first detection of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae strain belonging to sequence type 833 (ST833), collected in an Italian hospital from a patient coming from South America. Its blaKPC determinant was carried by a ColE1 plasmid, pKBuS13, that showed the Tn4401b::blaKPC-2 transposon inserted into the regulatory region of an Xer site-specific recombination locus. This interfered with the correct resolution of plasmid multimers into monomers, lowering plasmid stability and leading to overestimation of the number of plasmids harbored by a single host cell. Sequencing of the fragments adjacent to Tn4401b detected a region that did not have significant matches in databases other than the genome of a carbapenem-resistant Escherichia coli strain collected during the same year at a hospital in Boston. This is interesting in an epidemiologic context, as it suggests that despite the absence of tra genes and the instability under nonselective conditions, the circulation of pKBuS13 or of analogous plasmids might be wider than reported. PMID:26077252

  3. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Thomas Michiels

    2013-03-01

    Full Text Available The central nervous system (CNS harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i preventing neuroinvasion and infection of CNS cells; ii the identity of IFN-producing cells in the CNS; iii the antiviral activity of ISGs; and iv the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  4. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    Science.gov (United States)

    Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

    2013-01-01

    The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway. PMID:23503326

  5. Small-Molecule Inhibitors of the Type III Secretion System

    Directory of Open Access Journals (Sweden)

    Lingling Gu

    2015-09-01

    Full Text Available Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS, existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins.

  6. Radiative Type III Seesaw Model and its collider phenomenology

    CERN Document Server

    von der Pahlen, Federico; Restrepo, Diego; Zapata, Oscar

    2016-01-01

    We analyze the present bounds of a scotogenic model, the Radiative Type III Seesaw (RSIII), in which an additional scalar doublet and at least two fermion triplets of $SU(2)_L$ are added to the Standard Model (SM). In the RSIII the new physics (NP) sector is odd under an exact global $Z_2$ symmetry. This symmetry guaranties that the lightest NP neutral particle is stable, providing a natural dark matter (DM) candidate, and leads to naturally suppressed neutrino masses generated by a one-loop realization of an effective Weinberg operator. We focus on the region with the highest sensitivity in present and future LHC searches, with light scalar DM and at least one NP fermion triplet at the sub-TeV scale. This region allows for significant production cross-sections of NP fermion pairs at the LHC. We reinterpret a set of searches for supersymmetric particles at the LHC obtained using the package CheckMATE, to set limits on our model as a function of the masses of the NP particles and their Yukawa interactions. The...

  7. Spontaneous R-Parity Violating Type III Seesaw

    CERN Document Server

    Choubey, Sandhya

    2009-01-01

    We present a model where neutrino masses are generated by a combination of spontaneous R-parity violation and Type III seesaw. In addition to the usual MSSM particle content, our model consists of one extra triplet matter chiral superfield containing heavy SU(2) triplet fermions and its superpartners. R-parity is broken spontaneously when the sneutrinos associated with the one heavy neutrino as well as the three light neutrinos get vacuum expectation values, giving rise to the mixed $8\\times 8$ neutralino-neutrino mass matrix. We show that our model can comfortably explain all the existing neutrino oscillation data. Due to the presence of the triplet fermion, we have a pair of additional heavy charged leptons which mix with the standard model charged leptons and the charginos. This gives rise to a $6\\times 6$ chargino-charged lepton mass matrix, with 6 massive eigenstates. Finally we discuss about the different R-parity violating possible decay modes and the distinctive collider signatures which our model off...

  8. Identification of type II and III DDR2 inhibitors.

    Science.gov (United States)

    Richters, André; Nguyen, Hoang D; Phan, Trang; Simard, Jeffrey R; Grütter, Christian; Engel, Julian; Rauh, Daniel

    2014-05-22

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

  9. Evaluation of the Mangled Extremity Severity Score in Combat-Related Type III Tibia Fracture

    Science.gov (United States)

    2014-09-01

    ORIGINAL ARTICLE Evaluation of the Mangled Extremity Severity Score in Combat-Related Type III Open Tibia Fracture Andrew J. Sheean, MD,* Chad A...soldiers sustaining combat-related Gustilo–Anderson type III open tibia fractures. Design: Retrospective cohort study. Setting: Tertiary trauma center...Patients: Service Members with combat-related type III open tibia fractures occurring between 2003 and 2007 treated definitively in a US military medical

  10. Behind the lines–actions of bacterial type III effector proteins in plant cells

    OpenAIRE

    Büttner, Daniela

    2016-01-01

    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Ty...

  11. Synthesis of type III collagen by fibroblasts from the embryonic chick cornea

    OpenAIRE

    1980-01-01

    Synthesis of collagen types I, II, III, and IV in cells from the embryonic chick cornea was studied using specific antibodies and immunofluorescence. Synthesis of radioactively labeled collagen types I and III was followed by fluorographic detection of cyanogen bromide peptides on polyacrylamide slab gels and by carboxymethylcellulose chromatography followed by disc gel electrophoresis. Type III collagen had been detected previously by indirect immunofluorescence in the corneal epithelial cel...

  12. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    Science.gov (United States)

    Georgy, Gehan S; Nassar, Noha N; Mansour, Hanaa A; Abdallah, Dalaal M

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and

  13. Protein export through the bacterial flagellar type III export pathway.

    Science.gov (United States)

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. All rights reserved.

  14. Yersinia type III effectors perturb host innate immune responses

    Science.gov (United States)

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  15. Regulation of the Yersinia type III secretion system: traffic control

    Science.gov (United States)

    Dewoody, Rebecca S.; Merritt, Peter M.; Marketon, Melanie M.

    2013-01-01

    Yersinia species, as well as many other Gram-negative pathogens, use a type III secretion system (T3SS) to translocate effector proteins from the bacterial cytoplasm to the host cytosol. This T3SS resembles a molecular syringe, with a needle-like shaft connected to a basal body structure, which spans the inner and outer bacterial membranes. The basal body of the injectisome shares a high degree of homology with the bacterial flagellum. Extending from the T3SS basal body is the needle, which is a polymer of a single protein, YscF. The distal end of the needle serves as a platform for the assembly of a tip complex composed of LcrV. Though never directly observed, prevailing models assume that LcrV assists in the insertion of the pore-forming proteins YopB and YopD into the host cell membrane. This completes a bridge between the bacterium and host cell to provide a continuous channel through which effectors are delivered. Significant effort has gone into understanding how the T3SS is assembled, how its substrates are recognized and how substrate delivery is controlled. Arguably the latter topic is the least understood; however, recent advances have provided new insight, and therefore, this review will focus primarily on summarizing the current state of knowledge regarding the control of substrate delivery by the T3SS. Specifically, we will discuss the roles of YopK, as well as YopN and YopE, which have long been linked to regulation of translocation. We also propose models whereby the YopK regulator communicates with the basal body of the T3SS to control translocation. PMID:23390616

  16. Glycogen storage disease type III: modified Atkins diet improves myopathy.

    Science.gov (United States)

    Mayorandan, Sebene; Meyer, Uta; Hartmann, Hans; Das, Anibh Martin

    2014-11-28

    Frequent feeds with carbohydrate-rich meals or continuous enteral feeding has been the therapy of choice in glycogen storage disease (Glycogenosis) type III. Recent guidelines on diagnosis and management recommend frequent feedings with high complex carbohydrates or cornstarch avoiding fasting in children, while in adults a low-carb-high-protein-diet is recommended. While this regimen can prevent hypoglycaemia in children it does not improve skeletal and heart muscle function, which are compromised in patients with glycogenosis IIIa. Administration of carbohydrates may elicit reactive hyperinsulinism, resulting in suppression of lipolysis, ketogenesis, gluconeogenesis, and activation of glycogen synthesis. Thus, heart and skeletal muscle are depleted of energy substrates. Modified Atkins diet leads to increased blood levels of ketone bodies and fatty acids. We hypothesize that this health care intervention improves the energetic balance of muscles. We treated 2 boys with glycogenosis IIIa aged 9 and 11 years with a modified Atkins diet (10 g carbohydrate per day, protein and fatty acids ad libitum) over a period of 32 and 26 months, respectively. In both patients, creatine kinase levels in blood dropped in response to Atkins diet. When diet was withdrawn in one of the patients he complained of chest pain, reduced physical strength and creatine kinase levels rapidly increased. This was reversed when Atkins diet was reintroduced. One patient suffered from severe cardiomyopathy which significantly improved under diet. Patients with glycogenosis IIIa benefit from an improved energetic state of heart and skeletal muscle by introduction of Atkins diet both on a biochemical and clinical level. Apart from transient hypoglycaemia no serious adverse effects were observed.

  17. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Gehan S Georgy

    Full Text Available Cerebrolysin (CBL, a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF, is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i vehicle- (ii CBL- and (iii STZ diabetic-control as well as (iv STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%, which were associated by weight loss, elevated tumor necrosis factor (TNF-α and decreased insulin growth factor (IGF-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU, glycine, serotonin (5-HT and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti

  18. Type I and III procollagen propeptides in growth hormone-deficient patients

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J;

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

  19. A note on tilted Bianchi type VIh models: the type III bifurcation

    Science.gov (United States)

    Coley, A. A.; Hervik, S.

    2008-10-01

    In this note we complete the analysis of Hervik, van den Hoogen, Lim and Coley (2007 Class. Quantum Grav. 24 3859) of the late-time behaviour of tilted perfect fluid Bianchi type III models. We consider models with dust, and perfect fluids stiffer than dust, and eludicate the late-time behaviour by studying the centre manifold which dominates the behaviour of the model at late times. In the dust case, this centre manifold is three-dimensional and can be considered a double bifurcation as the two parameters (h and γ) of the type VIh model are varied. We therefore complete the analysis of the late-time behaviour of tilted ever-expanding Bianchi models of types I VIII.

  20. Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Mikkelsen, H; Bond, N J; Skindersoe, M E

    2009-01-01

    . This was confirmed by the detection of PcrV in the cellular and secreted fractions of biofilms, but not in those of planktonic cells. We also detected the type III effector proteins ExoS and ExoT in the biofilm effluent, but not in the supernatants of planktonic cells. Biofilm formation and type III secretion...

  1. 46 CFR 170.135 - Operating information for a vessel with Type III subdivision.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Operating information for a vessel with Type III... Operating Personnel § 170.135 Operating information for a vessel with Type III subdivision. (a) In addition to the information required in 46 CFR 170.110, the stability booklet of a passenger vessel with...

  2. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria

    DEFF Research Database (Denmark)

    Huizing, Marjan; Dorward, Heidi; Ly, Lien

    2010-01-01

    3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Her...

  3. 78 FR 9802 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated...

    Science.gov (United States)

    2013-02-12

    ... requirements to qualify as a Type III supporting organization that is operated in connection with one or more... Internal Revenue Service 26 CFR Part 1 RIN 1545-BG31; 1545-BL38 Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated; Correction AGENCY: Internal Revenue Service (IRS),...

  4. Behind the lines–actions of bacterial type III effector proteins in plant cells

    Science.gov (United States)

    Büttner, Daniela

    2016-01-01

    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Type III effectors also interfere with additional plant cellular processes including proteasome-dependent protein degradation, phytohormone signaling, the formation of the cytoskeleton, vesicle transport and gene expression. This review summarizes our current knowledge on the molecular functions of type III effector proteins with known plant target molecules. Furthermore, plant defense strategies for the detection of effector protein activities or effector-triggered alterations in plant targets are discussed. PMID:27526699

  5. Diagnosis of type III hyperlipoproteinemia by chromatography of plasma lipoproteins on columns containing agarose.

    Science.gov (United States)

    Shepherd, J; Packard, C J; Dryburgh, F J; Third, J L

    1975-12-01

    Agarose column chromatography has been used to separate plasma lipoproteins into very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Applied to the diagnosis of primary type III hyperlipoproteinemia, the procedure is capable of demonstrating three characteristic and specific changes from normality in the elution pattern of lipoproteins from patients with this condition. In the type III profile there is (a) incomplete separation of VLDL from putative LDL material, (b) early elution of the type III LDL with respect to a normal LDL marker, and (c) relative deficiency of type III LDL with elution characteristics of normal LDL. We advocate the use of this method in the diagnosis of type III hyperlipoproteinemia.

  6. Training improves oxidative capacity, but not function, in spinal muscular atrophy type III

    DEFF Research Database (Denmark)

    Madsen, Karen Lindhardt; Hansen, Regitze Sølling; Preisler, Nicolai

    2015-01-01

    INTRODUCTION: In this study we investigated the effect of 12 weeks of cycle ergometer training in patients with spinal muscular atrophy type III (SMA III), a hereditary motor neuron disease with progressive muscle weakness and atrophy. METHODS: Six SMA III patients and 9 healthy subjects completed......max (17 ± 2 to 21 ± 2 ml/kg/min, P SMA III without causing muscle...... damage, but it also induces significant fatigue. This warrants study into alternative training methods to improve exercise capacity in SMA III patients....

  7. Harnessing Type I and Type III CRISPR-Cas systems for genome editing.

    Science.gov (United States)

    Li, Yingjun; Pan, Saifu; Zhang, Yan; Ren, Min; Feng, Mingxia; Peng, Nan; Chen, Lanming; Liang, Yun Xiang; She, Qunxin

    2016-02-29

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are widespread in archaea and bacteria, and research on their molecular mechanisms has led to the development of genome-editing techniques based on a few Type II systems. However, there has not been any report on harnessing a Type I or Type III system for genome editing. Here, a method was developed to repurpose both CRISPR-Cas systems for genetic manipulation in Sulfolobus islandicus, a thermophilic archaeon. A novel type of genome-editing plasmid (pGE) was constructed, carrying an artificial mini-CRISPR array and a donor DNA containing a non-target sequence. Transformation of a pGE plasmid would yield two alternative fates to transformed cells: wild-type cells are to be targeted for chromosomal DNA degradation, leading to cell death, whereas those carrying the mutant gene would survive the cell killing and selectively retained as transformants. Using this strategy, different types of mutation were generated, including deletion, insertion and point mutations. We envision this method is readily applicable to different bacteria and archaea that carry an active CRISPR-Cas system of DNA interference provided the protospacer adjacent motif (PAM) of an uncharacterized PAM-dependent CRISPR-Cas system can be predicted by bioinformatic analysis.

  8. Types I and III procollagen extension peptides in serum respond to fracture in humans

    DEFF Research Database (Denmark)

    Joerring, S; Jensen, L T; Andersen, G R

    1992-01-01

    Markers of types I and III collagen turnover were measured in serial blood samples in 16 patients with a Colles' fracture. The collagen markers were the carboxy-terminal extension peptide of type I procollagen (PICP) and the amino-terminal extension peptide of type III procollagen (PIIINP......). Significant increases were found of PIIINP within 1 week and of PICP within 2 weeks. This sequential appearance of PIIINP and PICP was found to be in agreement with the appearance of types III and I collagen during early fracture healing as demonstrated in previous animal experimental studies. PICP had...... prove relevant as non-invasive markers of normal and pathological fracture healing in humans....

  9. Frontal Sinus Patency after Extended Frontal Sinusotomy Type III

    Science.gov (United States)

    Hajbeygi, Mansour; Nadjafi, Ali; Amali, Amin; Saedi, Babak; Sadrehosseini, Seyed Mousa

    2016-01-01

    Introduction: The surgical management of chronic frontal sinus disorders remains a challenge for rhinologists. The aim of this study was to evaluate the result of Draf III in a series of patients who underwent this procedure. Materials and Methods: Twenty patients were included in this study. Demographic data, history of prior surgery, asthma, aspirin sensitivity and Lund–Mackay score were recorded. A visual analog scale was used for frontal-related symptoms. Patients were followed for a mean duration of 17.5 months and the patency of the frontal sinus ostium was closely monitored. Results: Fifteen patients with chronic frontal sinusitis, two patients with mucoceles, two with malignancy, and one with osteoma underwent Draf III. The mean symptoms score significantly decreased from 5.9 to 3. No ostial closure was seen in the follow-up period. Among 15 patients with chronic frontal sinusitis, 12 had patent ostia of whom three had significant stenosis. All patients with mucocele and osteoma had patent ostia in the follow-up period but patients with sinonasal malignancy showed significant stenosis. Conclusion: Draf III frontal sinusotomy is successful in alleviating patient symptoms and the frontal sinus neo-ostium will remain patent in long-term follow-up of most patients. Revision surgery will be required in some cases, which seems to be related to the nature of the underlying chronic sinus diseases. PMID:27738610

  10. Type III Secretion: a Virulence Factor Delivery System Essential for the Pathogenicity of Burkholderia mallei

    OpenAIRE

    Ulrich, Ricky L; DeShazer, David

    2004-01-01

    By creating mutations in the Burkholderia mallei ATCC 23344 animal pathogen-like type III secretion system (TTSS), this study analyzes the correlation between type III secretion and the pathogenicity of ATCC 23344 in vivo. Mutagenesis demonstrated that a functional TTSS was required for the full pathogenicity of ATCC 23344 in the BALB/c mouse and Syrian hamster models of infection. However, vaccination with each mutant failed to elicit a protective immunity against challenge with wild-type AT...

  11. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Science.gov (United States)

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted.

  12. Second harmonic generation microscopy differentiates collagen type I and type III in COPD

    Science.gov (United States)

    Suzuki, Masaru; Kayra, Damian; Elliott, W. Mark; Hogg, James C.; Abraham, Thomas

    2012-03-01

    The structural remodeling of extracellular matrix proteins in peripheral lung region is an important feature in chronic obstructive pulmonary disease (COPD). Multiphoton microscopy is capable of inducing specific second harmonic generation (SHG) signal from non-centrosymmetric structural proteins such as fibrillar collagens. In this study, SHG microscopy was used to examine structural remodeling of the fibrillar collagens in human lungs undergoing emphysematous destruction (n=2). The SHG signals originating from these diseased lung thin sections from base to apex (n=16) were captured simultaneously in both forward and backward directions. We found that the SHG images detected in the forward direction showed well-developed and well-structured thick collagen fibers while the SHG images detected in the backward direction showed striking different morphological features which included the diffused pattern of forward detected structures plus other forms of collagen structures. Comparison of these images with the wellestablished immunohistochemical staining indicated that the structures detected in the forward direction are primarily the thick collagen type I fibers and the structures identified in the backward direction are diffusive structures of forward detected collagen type I plus collagen type III. In conclusion, we here demonstrate the feasibility of SHG microscopy in differentiating fibrillar collagen subtypes and understanding their remodeling in diseased lung tissues.

  13. Dietary management in glycogen storage disease type III : what is the evidence?

    NARCIS (Netherlands)

    Derks, Terry G. J.; Smit, G. Peter A.

    2015-01-01

    In childhood, GSD type III causes relatively severe fasting intolerance, classically associated with ketotic hypoglycaemia. During follow up, history of (documented) hypoglycaemia, clinical parameters (growth, liver size, motor development, neuromuscular parameters), laboratory parameters (glucose,

  14. Decameter type III bursts with positive and negative frequency drift rates

    Science.gov (United States)

    Melnik, V. N.; Brazhenko, A. I.; Konovalenko, A. A.; Briand, C.; Dorovskyy, V. V.; Zarka, P.; Frantzusenko, A. V.; Rucker, H. O.; Rutkevych, B. P.; Panchenko, M.; Zaqarashvili, T.; Shergelashvili, B.

    2013-09-01

    We report about observations of decameter type III bursts whose frequency drift rates vary their signs from negative to positive. Moreover drift rates of some bursts vary the sign some times. Positive drift rates for some bursts are changed from 0.44 MHz/s to 12 MHz/s. At the same time the negative drift rates of these bursts are standard values for decameter type III bursts. A possible interpretation of such phenomenon on the base of plasma mechanism of type III burst generation is discussed. The sense of this interpretation is that group velocity of type III electromagnetic waves generated by fast electrons at some conditions can be smaller than velocity of these electrons.

  15. Critical behavior of the Lyapunov exponent in type-III intermittency

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Llamoza, O. [Departamento de Fisica, FACYT, Universidad de Carabobo, Valencia (Venezuela); Centro de Fisica Fundamental, Grupo de Caos y Sistemas Complejos, Universidad de Los Andes, Merida 5251, Merida (Venezuela)], E-mail: llamoza@ula.ve; Cosenza, M.G. [Centro de Fisica Fundamental, Grupo de Caos y Sistemas Complejos, Universidad de Los Andes, Merida 5251, Merida (Venezuela); Ponce, G.A. [Departamento de Fisica, Universidad Nacional Autonoma de Honduras (Honduras); Departamento de Ciencias Naturales, Universidad Pedagogica Nacional Francisco Morazan, Tegucigalpa (Honduras)

    2008-04-15

    The critical behavior of the Lyapunov exponent near the transition to robust chaos via type-III intermittency is determined for a family of one-dimensional singular maps. Critical boundaries separating the region of robust chaos from the region where stable fixed points exist are calculated on the parameter space of the system. A critical exponent {beta} expressing the scaling of the Lyapunov exponent is calculated along the critical curve corresponding to the type-III intermittent transition to chaos. It is found that {beta} varies on the interval 0 {<=} {beta} < 1/2 as a function of the order of the singularity of the map. This contrasts with earlier predictions for the scaling behavior of the Lyapunov exponent in type-III intermittency. The variation of the critical exponent {beta} implies a continuous change in the nature of the transition to chaos via type-III intermittency, from a second-order, continuous transition to a first-order, discontinuous transition.

  16. Salter-Harris Type III and Type IV Combined Fracture of the Distal Femoral Epiphysis: A Case Report

    OpenAIRE

    Ali Aydin; Murat Topal; Kutsi Tuncer; Eyüp Şenocak

    2012-01-01

    Distal femoral physeal fractures are not common but have a high rate of complications. They generally follow one of the patterns described in the Salter-Harris classification. We present a case of combination of Salter-Harris type III and type IV injury. Our case was a 15-year-old boy who had a motor vehicle accident. There was swelling, ecchymosis, severe pain, and valgus deformity, because of medial proximal fracture fragment, on the left knee. We deemed that Salter-Harris type III and type...

  17. Salter-Harris Type III and Type IV Combined Fracture of the Distal Femoral Epiphysis: A Case Report.

    Science.gov (United States)

    Aydin, Ali; Topal, Murat; Tuncer, Kutsi; Senocak, Eyüp

    2012-01-01

    Distal femoral physeal fractures are not common but have a high rate of complications. They generally follow one of the patterns described in the Salter-Harris classification. We present a case of combination of Salter-Harris type III and type IV injury. Our case was a 15-year-old boy who had a motor vehicle accident. There was swelling, ecchymosis, severe pain, and valgus deformity, because of medial proximal fracture fragment, on the left knee. We deemed that Salter-Harris type III and type IV combination fracture in our case has not been previously reported. We prepared this paper in consideration of its contribution to the literature.

  18. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    Science.gov (United States)

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P types I/II, respectively. © 2016 British Society for Immunology.

  19. Critical scaling and type-III intermittent chaos in isolated rabbit resistance arteries

    Science.gov (United States)

    Griffith, T. M.; Parthimos, D.; Crombie, J.; Edwards, D. H.

    1997-12-01

    We have shown that spontaneous oscillations in flow in rabbit ear resistance arteries may sometimes exhibit behavior typical of type-III Pomeau-Manneville intermittency. The average number of oscillations per laminar length was related to a bifurcation parameter ɛ according to power-law scaling of the form ~ɛ-β. The critical exponent β was estimated as ~0.80, which is within the range reported for type-III intermittent chaos in nonbiological systems.

  20. Solar Micro-Type III Burst Storms and Long Dipolar Magnetic Field in the Outer Corona

    Science.gov (United States)

    Morioka, A.; Miyoshi, Y.; Iwai, K.; Kasaba, Y.; Masuda, S.; Misawa, H.; Obara, T.

    2015-08-01

    Solar micro-type III radio bursts are elements of the so-called type III storms and are characterized by short-lived, continuous, and weak emissions. Their frequency of occurrence with respect to radiation power is quite different from that of ordinary type III bursts, suggesting that the generation process is not flare-related, but due to some recurrent acceleration processes around the active region. We examine the relationship of micro-type III radio bursts with coronal streamers. We also explore the propagation channel of bursts in the outer corona, the acceleration process, and the escape route of electron beams. It is observationally confirmed that micro-type III bursts occur near the edge of coronal streamers. The magnetic field line of the escaping electron beams is tracked on the basis of the frequency drift rate of micro-type III bursts and the electron density distribution model. The results demonstrate that electron beams are trapped along closed dipolar field lines in the outer coronal region, which arise from the interface region between the active region and the coronal hole. A 22 year statistical study reveals that the apex altitude of the magnetic loop ranges from 15 to 50 RS. The distribution of the apex altitude has a sharp upper limit around 50 RS suggesting that an unknown but universal condition regulates the upper boundary of the streamer dipolar field.

  1. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system

    Institute of Scientific and Technical Information of China (English)

    Liang-liang Huang; Zhong-yang Liu; Jing-hui Huang; Zhuo-jing Luo

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinat-ing fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelin-ating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various develop-mental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunolfuorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunolfuorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10).

  2. Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems

    Science.gov (United States)

    Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C

    2017-01-01

    CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an ‘arms race’ in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems. PMID:28826484

  3. Structural and Biochemical Characterization of SrcA, a Multi-cargo Type III Secretion Chaperone in Salmonella Required for Pathogenic Association with a Host

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, C.; Zhang, K; Andres, S; Fnag, Y; Kaniuk, N; Hannemann, M; Brumell, J; Foster, L; Junop, M; Coombes, B

    2010-01-01

    Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2) is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 {angstrom} revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.

  4. Structural and biochemical characterization of SrcA, a multi-cargo type III secretion chaperone in Salmonella required for pathogenic association with a host.

    Directory of Open Access Journals (Sweden)

    Colin A Cooper

    2010-02-01

    Full Text Available Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2 is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 A revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2 and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.

  5. The extracellular matrix of Gadus morhua muscle contains types III, V, VI and IV collagens in addition to type I

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline; Lawson, M.A.

    2005-01-01

    Confocal microscopy and immuno‐histochemistry were used to examine collagens in the extracellular matrix of cod Gadus morhua swimming muscle. In addition to the well known presence of type I fibrous collagen, types III and VI were also found in the myocommata and the endomysium. The beaded collagen...

  6. Genomics and transcriptomics of Xanthomonas campestris species challenge the concept of core type III effectome.

    Science.gov (United States)

    Roux, Brice; Bolot, Stéphanie; Guy, Endrick; Denancé, Nicolas; Lautier, Martine; Jardinaud, Marie-Françoise; Fischer-Le Saux, Marion; Portier, Perrine; Jacques, Marie-Agnès; Gagnevin, Lionel; Pruvost, Olivier; Lauber, Emmanuelle; Arlat, Matthieu; Carrère, Sébastien; Koebnik, Ralf; Noël, Laurent D

    2015-11-18

    The bacterial species Xanthomonas campestris infects a wide range of Brassicaceae. Specific pathovars of this species cause black rot (pv. campestris), bacterial blight of stock (pv. incanae) or bacterial leaf spot (pv. raphani). In this study, we extended the genomic coverage of the species by sequencing and annotating the genomes of strains from pathovar incanae (CFBP 1606R and CFBP 2527R), pathovar raphani (CFBP 5828R) and a pathovar formerly named barbareae (CFBP 5825R). While comparative analyses identified a large core ORFeome at the species level, the core type III effectome was limited to only three putative type III effectors (XopP, XopF1 and XopAL1). In Xanthomonas, these effector proteins are injected inside the plant cells by the type III secretion system and contribute collectively to virulence. A deep and strand-specific RNA sequencing strategy was adopted in order to experimentally refine genome annotation for strain CFBP 5828R. This approach also allowed the experimental definition of novel ORFs and non-coding RNA transcripts. Using a constitutively active allele of hrpG, a master regulator of the type III secretion system, a HrpG-dependent regulon of 141 genes co-regulated with the type III secretion system was identified. Importantly, all these genes but seven are positively regulated by HrpG and 56 of those encode components of the Hrp type III secretion system and putative effector proteins. This dataset is an important resource to mine for novel type III effector proteins as well as for bacterial genes which could contribute to pathogenicity of X. campestris.

  7. Skin as marker for collagen type I/III ratio in abdominal wall fascia.

    Science.gov (United States)

    Peeters, E; De Hertogh, G; Junge, K; Klinge, U; Miserez, M

    2014-08-01

    An altered collagen metabolism could play an important role in hernia development. This study compared collagen type I/III ratio and organisation between hernia and control patients, and analysed the correlation in collagen type I/III ratio between skin and abdominal wall fascia. Collagen organisation was analysed in Haematoxylin-Eosin sections of anterior rectus sheath fascia, and collagen type I/III ratio, by crosspolarisation microscopy, in Sirius-Red sections of skin and anterior rectus sheath fascia, of 19 control, 10 primary inguinal, 10 recurrent inguinal, 13 primary incisional and 8 recurrent incisional hernia patients. Compared to control patients [7.2 (IQR = 6.8-7.7) and 7.2 (IQR = 5.8-7.9)], collagen type I/III ratio was significantly lower in skin and anterior rectus sheath fascia of primary inguinal [5.2 (IQR = 3.8-6.3) and 4.2 (IQR = 3.8-4.7)], recurrent inguinal [3.2 (IQR = 3.1-3.6) and 3.3 (IQR = 3-3.7)], primary incisional [3.5 (IQR = 3-3.9) and 3.4 (IQR = 3.3-3.6)] and recurrent incisional hernia [3.2 (IQR = 3.1-3.9) and 3.2 (IQR = 2.9-3.2)] patients; also incisional and recurrent inguinal hernia had lower ratio than primary inguinal hernia patients. Furthermore, collagen type I/III ratio was significantly correlated (r = 0.81; P fascia. Finally, collagen organisation was comparable between hernia and control patients. Furthermore, in both skin and abdominal wall fascia of hernia patients, collagen type I/III ratio was lower compared to control patients, with more pronounced abnormalities in incisional and recurrent inguinal hernia patients. Importantly, collagen type I/III ratio in skin was representative for that in abdominal wall fascia.

  8. Identification and characterization of a type III Trichomonas vaginalis virus in the protozoan pathogen Trichomonas vaginalis.

    Science.gov (United States)

    Bessarab, Irina N; Nakajima, Rui; Liu, Hsing-Wei; Tai, Jung-Hsiang

    2011-02-01

    A type III Trichomonas vaginalis virus, which may be involved in transcriptional regulation of the major surface protein gene P270 of the protozoan pathogen Trichomonas vaginalis, was purified and characterized in the present study. The complete 4844-base-pair complementary DNA sequence of the viral genome reveals overlapping cap and pol genes with a putative ribosomal frame-shifting signal within the overlap region. The type III virus is related more closely to the type II virus than to the type I virus in the sequence of its ribosomal frameshift signal and in its capsid protein. Phylogenetic analysis revealed that these viruses could be grouped in the same clade as a genus distantly related to other genera in the family Totiviridae. Virus-induced P270 gene expression was only evident in Trichomonas vaginalis cells infected with either a type II or type III virus, but not with a type I virus. These findings suggest that transcription of the P270 gene is likely regulated by viral factors common to type II and type III viruses and thus provides important information for future investigation of virus-host interactions.

  9. Lack of the type III epidermal growth factor receptor mutation in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Olsen, Dorte Aalund; Nielsen, Jens Nederby;

    2007-01-01

    network are being investigated and mutations in the EGFR gene have been identified. The type III epidermal growth factor receptor, a tumour-specific, ligand independent, constitutively activated form of EGFR, might contribute to the malignant phenotype in CRC and may be a potential target for anticancer...... therapy. The aim of the present study was to investigate the presence of EGFRvIII in CRC by PCR and protein analysis. MATERIALS AND METHODS: The study included 79 colorectal cancer patients for PCR analysis and 50 patients for protein analysis by Western blots, in two different laboratories. RESULTS......: No type III mutations were detected in our material. CONCLUSION: The EGFRvIII mutations are rare in colorectal adenocarcinomas and overall probability does not appear to contribute to the malignant phenotype of this disease....

  10. DISTRIBUTION OF COLLAGENS TYPE-I, TYPE-III AND TYPE-V IN THE PANCREAS OF RAT, DOG, PIG AND MAN

    NARCIS (Netherlands)

    VANDEIJNEN, JHM; VANSUYLICHEM, PTR; WOLTERS, GHJ; VANSCHILFGAARDE, R

    1994-01-01

    The presence of collagens type I, type III and type V was determined immunohistochemically in pancreatic tissue of rat, pig, dog and man. The reaction to anti-collagen type I is weak (pig, dog) or moderate (rat, man) in the peri-insular region and in the lobar, lobular and acinar septa, whereas the

  11. Methods for enhancing P-type doping in III-V semiconductor films

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Feng; Stringfellow, Gerald; Zhu, Junyi

    2017-08-01

    Methods of doping a semiconductor film are provided. The methods comprise epitaxially growing the III-V semiconductor film in the presence of a dopant, a surfactant capable of acting as an electron reservoir, and hydrogen, under conditions that promote the formation of a III-V semiconductor film doped with the p-type dopant. In some embodiments of the methods, the epitaxial growth of the doped III-V semiconductor film is initiated at a first hydrogen partial pressure which is increased to a second hydrogen partial pressure during the epitaxial growth process.

  12. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria

    DEFF Research Database (Denmark)

    Huizing, Marjan; Dorward, Heidi; Ly, Lien;

    2010-01-01

    3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Her...... we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown...

  13. On the three harmonics of solar type III bursts at the decameter wavelengths

    Science.gov (United States)

    Brazhenko, Anatolii; Pylaev, Oleg; Melnik, Valentin; Konovalenko, Alexandr; Zaqarashvili, Teimuraz; Rucker, Helmut; Frantsuzenko, Anatolii; Dorovskyy, Vladimir

    2014-05-01

    Harmonic structure of type III bursts are explained in terms of plasma emission mechanism. The second harmonic emission is well known. But there are theoretical papers about the third harmonic of type III bursts. And there were observations of the third harmonic of such types of bursts as U, J, V, II. We observed triple type III bursts where frequency ratio is close to 1:2:3. They are structures where type III emission is repeated at the double and triple frequencies. Incidentally, components of triple type III bursts are not only standard type III but also type IIIb bursts. We registered 30 triple bursts during 2011 and 2012 years. Observations were made by radio telescope URAN-2, Poltava, Ukraine. It enables polarization measurements at the frequencies 8 - 32 MHz. URAN-2 allows registration of radio emission with time and frequency resolution 10 ms and 4 kHz correspondingly. We analyze properties of the components of triple bursts and their dependencies on frequency, type of burst and on the position of the component within the triplet. The main properties of the components of triple bursts such as duration and drift rate are similar to those of standard type III and IIIb bursts. We find usual for type III bursts dependencies such as follow: duration decreases with frequency, the type IIIb bursts have always smaller duration at the same frequencies, all bursts drift from high to low frequencies. But we also find the linear dependence of drift rate on frequency. All components of a trio have the same sign of polarization. Polarization of the first component is always the highest in triple bursts. It corresponds to the generally accepted viewpoint about the first harmonic emission. The second and the third components of trio have low polarization. It is typical for the second and the third harmonics according to the plasma radiation mechanism. We discuss possible emission mechanisms and theoretical aspects of observed dependencies. The most of detected regularities

  14. NCEP-ATP III and IDF criteria for metabolic syndrome predict type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Eva Sulistiowati

    2016-05-01

    Full Text Available Background Subjects with metabolic syndrome (MetS have a greater risk for acquiring type 2 diabetes mellitus (type 2 DM. The MetS criteria usually used are those of the National Cholesterol Education Program Expert Panel (NCEP and Adult Treatment Panel III (ATP III and of the International Diabetes Federation (IDF. This study aimed to evaluate the modified NCEP-ATP III and IDF criteria as predictor of type 2 DM among subjects with MetS.   Methods A cohort study was conducted among 4240 subjects with MetS. MetS was determined according to the modified NCEP-ATP III and IDF criteria. The study followed up 3324 non-diabetic subjects of the cohort study of non-communicable disease (NCD risk factors (NCD study during a 2-year period. Type 2 DM was determined from the diagnosis by health personnel or from fasting blood glucose of ≥126 mg/dL or blood glucose of ≥200 mg/dL, 2 hours after 75g glucose loading.   Results The MetS prevalence based on modified NCEP ATP III and IDF criteria in non-DM subjects was 17.1% and 15.6%, respectively. The risk for DM in subjects with MetS using modified NCEP ATP III and IDF criteria was 4.7 (CI 95%: 3.4-6.5 and 4.1 (CI 95%: 3.0-5.7, respectively.   Conclusions Both MetS criteria can be used as predictors of the occurrence of DM type 2, but the modified NCEP-ATP III is more properly applied than the IDF criteria in subjects with MetS. Screening programs and routine monitoring of MetS components are required for early detection of type 2 DM.

  15. Serial audiometry and speech recognition findings in Finnish Usher syndrome type III patients.

    NARCIS (Netherlands)

    Plantinga, R.F.; Kleemola, L.; Huygen, P.L.M.; Joensuu, T.; Sankila, E.M.; Pennings, R.J.E.; Cremers, C.W.R.J.

    2005-01-01

    Audiometric features, evaluated by serial pure tone audiometry and speech recognition tests (n = 31), were analysed in 59 Finnish Usher syndrome type III patients (USH3) with Finmajor/Finmajor (n = 55) and Finmajor/Finminor (n = 4) USH3A mutations. These patients showed a highly variable type and de

  16. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    Science.gov (United States)

    2013-01-01

    Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments. PMID:23331413

  17. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

    Science.gov (United States)

    Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

    2015-08-01

    Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; Ptriglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

  18. Translational regulation of Yersinia enterocolitica mRNA encoding a type III secretion substrate.

    Science.gov (United States)

    Kopaskie, Karyl S; Ligtenberg, Katherine Given; Schneewind, Olaf

    2013-12-06

    Yersinia enterocolitica type III secretion machines transport YopQ and other Yop effectors into host immune cells. YopD and its chaperone LcrH are essential components of the Yersinia type III pathway, enabling effector translocation into host cells. YopD, LcrH, and YscM1 also regulate yop expression post-transcriptionally in response to environmental signals; however, the molecular mechanisms for this regulation and Yop secretion are unknown. We show here that YopD associates with 30 S ribosomal particles in a manner requiring LcrH. When added to ribosomes, YopD, LcrH, and YscM1 block the translation of yopQ mRNA. We propose a model whereby LcrH-dependent association of YopD with 30 S ribosomal particles enables YscM1 to block yopQ translation unless type III machines are induced to secrete the effector.

  19. The heliocentric radial variation of plasma oscillations associated with type III radio bursts

    Science.gov (United States)

    Gurnett, D. A.; Anderson, R. R.; Scarf, F. L.; Kurth, W. S.

    1978-01-01

    A survey is presented of all of the electron plasma oscillation events found to date in association with low-frequency type III solar radio bursts using approximately 9 years of observations from the Imp 6 and 8, Helios 1 and 2, and Voyager 1 and 2 spacecraft. Plasma oscillation events associated with type III radio bursts show a pronounced increase in both the intensity and the frequency of occurrence with decreasing heliocentric radial distance. This radial dependence explains why intense electron plasma oscillations are seldon observed in association with type III radio bursts at the orbit of the earth. Possible interpretations of the observed radial variation in the plasma oscillation intensity are considered.

  20. Studying the evolution of a type III radio from the Sun up to 1 AU

    Science.gov (United States)

    Mann, Gottfried; Breitling, Frank; Vocks, Christian; Fallows, Richard; Melnik, Valentin; Konovalenko, Alexander

    2017-04-01

    On March 16, 2016, a type III burst was observed with the ground-based radio telescopes LOFAR and URAN-2 as well as with the radiospectrometer aboard the spacecraft WIND.It started at 80 MHz at 06:37 UT and reached 50 kHz after 23 minutes. A type III burst are considered as the radio signature of an electron beam travelling from the corona into the interplanetary space. The energetic electrons carrying the beam excites Langmuir waves, which convert into radio waves by wave-particle interaction. The relationship between the drift rate and the frequency as derived from the dynamic radio spectra reveals that the velocity of the electrons generating the radio waves of the type III burst is increasing with increasing distance from the center of the Sun.

  1. Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

    Science.gov (United States)

    Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

    2011-11-01

    Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia.

  2. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity

    DEFF Research Database (Denmark)

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina

    2008-01-01

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda w...

  3. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity

    DEFF Research Database (Denmark)

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina;

    2008-01-01

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda w...

  4. Cardiac function in types II and III spinal muscular atrophy: should we change standards of care?

    Science.gov (United States)

    Bianco, Flaviana; Pane, Marika; D'Amico, Adele; Messina, Sonia; Delogu, Angelica Bibiana; Soraru, Gianni; Pera, Maria Carmela; Mongini, Tiziana; Politano, Luisa; Baranello, Giovanni; Vita, Gianluca; Tiziano, Francesco Danilo; Morandi, Lucia; Bertini, Enrico; Mercuri, Eugenio

    2015-02-01

    In the last years, there has been increasing evidence of cardiac involvement in spinal muscular atrophy (SMA). Autonomic dysfunction has been reported in animal models and in several patients with types I and III SMA, these findings raising the question whether heart rate should be routinely investigated in all SMA patients. The aim of our study was to detect possible signs of autonomic dysfunction and, more generally, of cardiac involvement in types II and III SMA. We retrospectively reviewed 24-hour electrocardiography (ECG) in 157 types II and III SMA patients (age range, 2-74 years). Of them, 82 also had echocardiography. None of the patients had signs of bradycardia, atrial fibrillation, or the other previously reported rhythm disturbances regardless of the age at examination or the type of SMA. Echocardiography was also normal. There were no signs of congenital cardiac defects with the exception of one patient with a history of ventricular septal defects. Our results suggest that cardiac abnormalities are not common in type II and type III SMA. These findings provide no evidence to support a more accurate cardiac surveillance or changes in the existing standards of care. Georg Thieme Verlag KG Stuttgart · New York.

  5. Type III Radio Bursts and the Structure of the Inner Heliosphere

    Science.gov (United States)

    Reiner, M. J.

    2003-12-01

    Type III solar radio bursts provide important information on the origin, acceleration, and propagation of particles associated with solar flares and coronal shocks. Since these radio emissions are generated by the plasma emission mechanism, observations of these solar radio transients also provide remote sensing of the plasma conditions in the corona and of the magnetic and plasma structure of the inner heliosphere. In this talk I will review the progress of type III research from their discovery in the late 40s to the most recent advances from low-frequency spacecraft observations, primarily from ISEE-3, Wind and Ulysses.

  6. Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, L T; Hørslev-Petersen, K; Toft, P

    1990-01-01

    values were observed on the third to seventh postinfarction day. The individual peak changes were correlated to infarction size calculated from serum CK-MB and serum lactate dehydrogenase (p = 0.60, p = 0.02). The changes in distribution of PIIINP-related antigens in serum after gel chromatography were...... similar to changes observed during wound healing in humans. PIIINP is cleaved off procollagen type III during the biosynthesis of type III collagen, which characterizes the early stages of repair and inflammation. Our findings suggest that serum PIIINP reflects the repair processes and scar formation...

  7. Perfect simulation and moment properties for the Matérn type III process

    DEFF Research Database (Denmark)

    Møller, Jesper; Huber, Mark L.; Wolpert, Robert L.

    2010-01-01

    In a seminal work, Bertil Matérn introduced several types of processes for modeling repulsive point processes. In this paper an algorithm is presented for the perfect simulation of the Matérn III process within a bounded window in , fully accounting for edge effects. A simple upper bound on the m......In a seminal work, Bertil Matérn introduced several types of processes for modeling repulsive point processes. In this paper an algorithm is presented for the perfect simulation of the Matérn III process within a bounded window in , fully accounting for edge effects. A simple upper bound...

  8. Three cross leg flaps for lower leg reconstruction of Gustilo type III C open fracture

    Directory of Open Access Journals (Sweden)

    Kazufumi Sano

    2016-01-01

    Full Text Available A 60 year old male had Gustilo type III C open fracture of the right lower leg. After radical debridement, the large open defect including certain loss of the bone tissue was successfully augmented and covered, by consecutive three cross-leg flaps, which consisted of the free rectus abdominis musculocutaneous flap, the fibula osteocutaneous flap and the conventional sural flap. Although indication for amputation or preservation is decided with multiple factors in each case, a strategic combination of cross-leg flap, free flap, external fixation and vascular delay could increase the potential of preservation of the lower leg with even disastrous Gustilo type III C.

  9. Conservative Management of Type III Dens in Dente Using Cone Beam Computed Tomography

    Directory of Open Access Journals (Sweden)

    K Pradeep

    2012-01-01

    Full Text Available Dens in dente, also known as dens invaginatus, dilated composite odontoma, or deep foramen caecum, is a developmental malformation that usually affects maxillary incisor teeth, particularly lateral incisors. It may occur in teeth anywhere within the jaws, other locations are comparatively rare. It can occur within both the crown and the root, although crown invaginations are more common. The use of cone beam computed tomography (CBCT is very helpful in endodontic diagnosis of complex anatomic variations. In this case we demonstrate the use of CBCT in the evaluation and endodontic management of a Type III dens in dente (Oehler′s Type III.

  10. Crystal structure of the Yersinia type III secretion protein YscE

    Energy Technology Data Exchange (ETDEWEB)

    Phan, Jason; Austin, Brian P.; Waugh, David S. (NIH)

    2010-12-06

    The plague-causing bacterium Yersinia pestis utilizes a contact-dependent (type III) secretion system (T3SS) to transport virulence factors from the bacterial cytosol directly into the interior of mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. The type III secretion apparatus is composed of 20-25 different Yersinia secretion (Ysc) proteins. We report here the structure of YscE, the smallest Ysc protein, which is a dimer in solution. The probable mode of oligomerization is discussed.

  11. Salter-Harris Type III and Type IV Combined Fracture of the Distal Femoral Epiphysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    2012-01-01

    Full Text Available Distal femoral physeal fractures are not common but have a high rate of complications. They generally follow one of the patterns described in the Salter-Harris classification. We present a case of combination of Salter-Harris type III and type IV injury. Our case was a 15-year-old boy who had a motor vehicle accident. There was swelling, ecchymosis, severe pain, and valgus deformity, because of medial proximal fracture fragment, on the left knee. We deemed that Salter-Harris type III and type IV combination fracture in our case has not been previously reported. We prepared this paper in consideration of its contribution to the literature.

  12. Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

    Science.gov (United States)

    Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

    2011-04-01

    Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

  13. Concurrent Occurrence of Type II and Type III Endoleak of Abdominal Aortic Aneurysm Stent Graft: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Su; Hong, Seong Sook; Kim, Jung Hoon; Kim, Yong Jae; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2009-12-15

    Endoleak is an important complication following stent grafts for abdominal aortic aneurysms. Here we describe ultrasonography findings in an 86-year-old man including doppler ultrasonography and CT scan in an unusual and interesting case of the concurrent occurrence of a type II endoleak that originated from the left accessory renal artery and a type III endoleak due to shaft fracture of the stent

  14. Collagen Type III and VI Turnover in Response to Long-Term Immobilization

    DEFF Research Database (Denmark)

    Sun, Shu; Henriksen, Kim; Karsdal, Morten A

    2015-01-01

    BACKGROUND: Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide...... biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated...... the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. RESULTS: Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected...

  15. The effects of K2SO4 solution on the compressive strength of dental gypsum type III

    Science.gov (United States)

    Adeilina, T.; Triaminingsih, S.; Indrani, D. J.

    2017-08-01

    Dental gypsum type III is used as a material for manufacturing working models of dentures. The aim of this study was to identify the effects of the addition of a K2SO4 solution on the compressive strength of gypsum type III. A compressive strength test was performed using a universal testing machine with a crosshead speed of 1 mm/min. The data were analyzed using a one-way ANOVA. The results showed that the compressive strength of gypsum type III with a 1.5% K2SO4 solution added was higher than for gypsum type III alone but lower than the compressive strength of gypsum type IV.

  16. Tracking Type III Radio Burst Sources in the Solar Corona by Heliographic Means

    Science.gov (United States)

    Koval, A. A.; Stanislavsky, A. A.; Konovalenko, A. A.; Volvach, Ya. S.

    We present the preliminary results of heliographic measurements of solar type III radio bursts in the low-frequency range (16.5-33 MHz) using the UTR-2 radio heliograph. The radio astronomy tools permit us to obtain two-dimensional spatial structures of burst sources in dependence of frequency and time. Each heliogram consists of 40 pixels (beams) as a result of the serial sweep in UV-plane wherein signals of each beam are recorded in a dynamic spectrum with both high temporal (˜ 2.482 ms) and top spectral (˜ 4 kHz) resolutions. The rate of output heliograph is one image per 3 seconds. Over a session in April, 2013 many type III radio and IIIb-III bursts were observed. On the heliograms the source motion direction in the upper corona is clearly detectable. The heliogram features are discussed.

  17. Angular Study of the III Type Solar Bursts by Ukrainian Decameter Heliograph of UTR-2

    Science.gov (United States)

    Koval, Artem; Stanislavsky, Aleksander; Konovalenko, Aleksander

    2014-05-01

    Solar radio bursts are attractive manifestations of solar activity. They contain useful information about physical processes in solar corona. The type III radio bursts are the most frequent events among many different types of solar bursts studied since middle of the last century. The type III bursts are generated by beams of fast electrons (beams velocity ~ 0.3c) ejected into the corona and propagated through coronal plasma to interplanetary medium. It is assumed that such an electron beam passing coronal plasma generates plasma waves that converse to electromagnetic waves registered as type III radio bursts. They are observed in a wide frequency range from 1 GHz to tens kHz. In particular, the decameter emission (10-30 MHz) of III type bursts arises at heights about 2-3 solar radii from the center of the Sun. In the last decades the various ground-based, satellite and spacecraft observations have provided detailed information about features of the bursts. Due to non-thermal emission mechanism their intensity can be very high that allows ones to record the bursts even by amateur radio astronomers with help of elementary antennas (for example, half-wave dipole) and simple radio equipment. At dynamic spectra the type III radio bursts are characterized by very fast frequency drifts. Usually, the analysis of such two-dimensional spectrograms reveals also duration and intensity of the events in time and frequency; if the antenna facilities permit, as well as degree of polarization. It should be noticed that the observations of angular three-dimensional structure of the burst source are also of great interest. Our knowledge about angular structure of type III radio bursts in decameter wavelengths was very restricted because of the absence of appropriate radio astronomy instruments. Recently, the difficulty has been overcome by means of the UTR-2 radio telescope (Kharkiv, Ukraine) in heliographic modes. It was successfully used for heliographic observations of solar

  18. Domain III regulates N-type (CaV2.2) calcium channel closing kinetics

    Science.gov (United States)

    Yarotskyy, Viktor; Gao, Guofeng; Peterson, Blaise Z.

    2012-01-01

    CaV2.2 (N-type) and CaV1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activation-deactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channel-like deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with R-roscovitine, which is a trisubstituted purine that slows N-channel deactivation by exclusively binding to activated N-channels. L-channels lack this response to roscovitine, which allowed us to use N-L chimeras to test the role of domain III in roscovitine modulation of N-channel deactivation. In support of our hypothesis, all chimeric channels containing the N-channel domain III responded to roscovitine with slowed deactivation, while those chimeric channels with L-channel domain III did not. Thus a combination of kinetic and pharmacological evidence supports the hypothesis that domain III is an important regulator of N-channel closing. Our results support specialization of gating functions among calcium channel domains. PMID:22205645

  19. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    Science.gov (United States)

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species.

  20. Impact of Type III Secretion Effectors and of Phenoxyacetamide Inhibitors of Type III Secretion on Abscess Formation in a Mouse Model of Pseudomonas aeruginosa Infection.

    Science.gov (United States)

    Berube, Bryan J; Murphy, Katherine; Torhan, Matthew C; Bowlin, Nicholas O; Williams, John D; Bowlin, Terry L; Moir, Donald T; Hauser, Alan R

    2017-08-14

    Pseudomonas aeruginosa is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or micro-abscess formation. The rising incidence of multi-drug resistance among P. aeruginosa isolates has increased both the economic burden and the morbidity and mortality associated with P. aeruginosa disease and necessitates a search for novel therapeutics. Previous work from our group detailed novel phenoxyacetamide inhibitors that block type III secretion and injection into host cells in vitro In this study, we used a murine abscess model of P. aeruginosa infection to test in vivo efficacy of these compounds against the P. aeruginosa type III secretion system (T3SS). Bacteria used the T3SS to intoxicate infiltrating neutrophils to establish abscesses. Despite this antagonism, sufficient numbers of functioning neutrophils remained for proper containment of abscesses, as neutrophil depletion resulted in increased abscess size, formation of dermonecrotic lesions on the skin, and dissemination of P. aeruginosa to internal organs. Consistent with the specificity of the T3SS/neutrophil interaction, P. aeruginosa lacking a functional T3SS was fully capable of causing abscesses in a neutropenic host. Phenoxyacetamide inhibitors attenuated abscess formation and aided in immune clearance of bacteria. Finally, a P. aeruginosa strain resistant to the phenoxyacetamide compound was fully capable of causing abscess formation even in the presence of the T3SS inhibitors. Together our results further define the role of type III secretion in murine abscess formation and demonstrate the in vivo efficacy of phenoxyacetamide inhibitors in P. aeruginosa infection. Copyright © 2017 American Society for Microbiology.

  1. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

    Science.gov (United States)

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G.; Muñiz, Jesus; Ramirez-Archila, Mario V.; Sanchez-Pastor, Enrique A.; Andrade, Felipa; Soñanez-Organis, Jose G.; Moran-Palacio, Edgar F.; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. PMID:25147829

  2. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

    Directory of Open Access Journals (Sweden)

    Sarai Limon-Miranda

    2014-01-01

    Full Text Available The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I and collagen III (Col III mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum.

  3. Type III restriction endonucleases translocate DNA in a reaction driven by recognition site-specific ATP hydrolysis.

    OpenAIRE

    Meisel, A.; Mackeldanz, P; Bickle, T A; Krüger, D H; Schroeder, C.

    1995-01-01

    Type III restriction/modification systems recognize short non-palindromic sequences, only one strand of which can be methylated. Replication of type III-modified DNA produces completely unmethylated recognition sites which, according to classical mechanisms of restriction, should be signals for restriction. We have shown previously that suicidal restriction by the type III enzyme EcoP15I is prevented if all the unmodified sites are in the same orientation: restriction by EcoP15I requires a pa...

  4. 77 FR 76382 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Science.gov (United States)

    2012-12-28

    .... Background This document contains amendments to the Income Tax Regulations (26 CFR part 1) and Foundation... Form 990, ``Return of Organization Exempt from Income Tax,'' or other annual information return... Pension Protection Act of 2006. The regulations will affect Type III supporting organizations and their...

  5. Integrated scenario with type-III ELMy H-mode edge: extrapolation to ITER

    NARCIS (Netherlands)

    Rapp, J.; Corre, Y.; Andrew, Y.; M.R. de Baar,; Beurskens, M.; Brezinsek, S.; Brix, M.; Devaux, S.; Eich, T.; Felton, R.; Fundamenski, W.; Giroud, C.; Howell, D.; Huber, A.; Jachmich, S.; Joffrin, E.; Korotkov, A.; Matthews, G. F.; McDonald, D. C.; Meigs, A.; Monier-Garbet, P.; Morgan, P.; Nunes, I.; van Rooij, G. J.; Sauter, O.; Stamp, M. F.; Telesca, G.; de Vries, P. C.; Zagorski, R.

    2009-01-01

    One of the most severe problems for fusion reactors is the power load on the plasma facing components. The challenge is to develop operation scenarios, which combine sufficient energy confinement with benign heat loads to the plasma facing components. The radiative type-III ELMy H-mode seems a possi

  6. IpaD is localized at the tip of the Shigella flexneri type III secretion apparatus

    NARCIS (Netherlands)

    Sani, Musa; Botteaux, Anne; Parsot, Claude; Sansonetti, Philippe; Boekema, Egbert J.; Allaoui, Abdelmounaaïm

    2007-01-01

    Type III secretion (T3S) systems are used by numerous Gram-negative pathogenic bacteria to inject virulence proteins into animal and plant host cells. The core of the T3S apparatus, known as the needle complex, is composed of a basal body transversing both bacterial membranes and a needle protruding

  7. Structure of Spa15, a type III secretion chaperone from Shigella flexneri with broad specificity

    NARCIS (Netherlands)

    Eerde, André van; Hamiaux, Cyril; Pérez, Javier; Parsot, Claude; Dijkstra, Bauke W.

    2004-01-01

    Type III secretion (TTS) systems are used by many Gram-negative pathogens to inject virulence proteins into the cells of their hosts. Several of these virulence effectors require TTS chaperones that maintain them in a secretion-competent state. Whereas most chaperones bind only one effector, Spa15 f

  8. Weapons of Mass Secretion : The Type III Secretion System of Shigella flexneri

    NARCIS (Netherlands)

    Sani, Musa

    2007-01-01

    In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications, fa

  9. The aminoterminal propeptide of type III procollagen provides new information on prognosis after acute myocardial infarction

    DEFF Research Database (Denmark)

    Høst, N B; Jensen, L T; Bendixen, P M;

    1995-01-01

    The aim of the study was to examine sequential changes in serum levels of the aminoterminal propeptide of type III procollagen (S-PIIINP) after acute myocardial infarction (AMI), and to assess the value of S-PIIINP as a predictor of outcome. The study group comprised 74 patients with AMI, and 24...

  10. Anomalous Statistics for Type-III Intermittency in a 1D Map

    DEFF Research Database (Denmark)

    J., Laugesen; Carlsson, N.; Mosekilde, Erik

    1997-01-01

    The statistics for the distribution of laminar phases in type-III intermittency is examined for a symmetric bimodal map. Due to a strongly nonuniform reinjection process, characteristic deviations from normal statistics are observed. There is an enhancement of relatively long laminar phases...

  11. Aquatic Therapy for a Child with Type III Spinal Muscular Atrophy: A Case Report

    Science.gov (United States)

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-01-01

    Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons. This case report describes an aquatic therapy program and the outcomes for a 3-year-old girl with type III SMA. Motor skills were examined using the 88-item Gross Motor Function Measure (GMFM), the Peabody Developmental Motor Scales…

  12. Perfect simulation and moment properties for the Matérn type III process

    DEFF Research Database (Denmark)

    Møller, Jesper; Huber, Mark L.; Wolpert, Robert L.

    In a seminal work, Bertil Matérn introduced several types of processes for modeling repulsive point processes. In this paper an algorithm is presented for the perfect simulation of the Mat´ern III process within a bounded window in Rd fully accounting for edge effects. A simple upper bound...

  13. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT

    1999-01-01

    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy hav

  14. A bacterial pathogen uses distinct type III secretion systems to alternate between host kingdoms

    Science.gov (United States)

    Plant and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (Pnss), the causative agent of Stewart’s bacterial wilt and...

  15. Cloning and characterization of type III iodothyronine deiodinase from the fish Oreochromis niloticus

    NARCIS (Netherlands)

    J.P. Sanders (Jo); S. van der Geyten; E. Kaptein (Ellen); V.M. Darras (Veerle); E.R. Kuhn; J.L. Leonard; T.J. Visser (Theo)

    1999-01-01

    textabstractType III iodothyronine deiodinase (D3) catalyzes the inner ring deiodination (IRD) of T4 and T3 to the inactive metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2), respectively. Here we describe the cloning and characterization of complementary DNA (cDNA) co

  16. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue

    Directory of Open Access Journals (Sweden)

    Pawel Olczyk

    2013-01-01

    Full Text Available Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues. Burn wounds were inflicted on pigs, chosen for the evaluation of wound repair because of many similarities between pig and human skin. Isolated collagen types I and III were estimated by the surface plasmon resonance method with a subsequent collagenous quantification using electrophoretic and densitometric analyses. Propolis burn treatment led to enhanced collagens and its components expression, especially during the initial stage of the study. Less expressed changes were observed after silver sulfadiazine (AgSD application. AgSD and, with a smaller intensity, propolis stimulated accumulation of collagenous degradation products. The assessed propolis therapeutic efficacy, throughout quantitatively and qualitatively analyses of collagen types I and III expression and degradation in wounds matrix, may indicate that apitherapeutic agent can generate favorable biochemical environment supporting reepithelization.

  17. Structure of Spa15, a type III secretion chaperone from Shigella flexneri with broad specificity

    NARCIS (Netherlands)

    Eerde, André van; Hamiaux, Cyril; Pérez, Javier; Parsot, Claude; Dijkstra, Bauke W.

    2004-01-01

    Type III secretion (TTS) systems are used by many Gram-negative pathogens to inject virulence proteins into the cells of their hosts. Several of these virulence effectors require TTS chaperones that maintain them in a secretion-competent state. Whereas most chaperones bind only one effector, Spa15

  18. IpaD is localized at the tip of the Shigella flexneri type III secretion apparatus

    NARCIS (Netherlands)

    Sani, Musa; Botteaux, Anne; Parsot, Claude; Sansonetti, Philippe; Boekema, Egbert J.; Allaoui, Abdelmounaaïm

    2007-01-01

    Type III secretion (T3S) systems are used by numerous Gram-negative pathogenic bacteria to inject virulence proteins into animal and plant host cells. The core of the T3S apparatus, known as the needle complex, is composed of a basal body transversing both bacterial membranes and a needle protruding

  19. Weapons of Mass Secretion : The Type III Secretion System of Shigella flexneri

    NARCIS (Netherlands)

    Sani, Musa

    2007-01-01

    In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications,

  20. An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis

    OpenAIRE

    Muro, Andrés F.; Moretti, Federico A.; Moore, Bethany B.; Yan, Mei; Atrasz, Rachelle G.; Wilke, Carol A.; Flaherty, Kevin R.; Martinez, Fernando J.; Tsui, Jessica L.; Sheppard, Dean; Baralle, Francisco E.; Toews, Galen B.; White, Eric S.

    2007-01-01

    Rationale: Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen.

  1. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.

    Science.gov (United States)

    Tomoeda, K; Awata, H; Matsuura, T; Matsuda, I; Ploechl, E; Milovac, T; Boneh, A; Scott, C R; Danks, D M; Endo, F

    2000-11-01

    The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD may lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been postulated that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency. Hawkinsin is a sulfur amino acid identified as (2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid. Patients with hawkinsinuria excrete this metabolite in their urine throughout their life, although symptoms of metabolic acidosis and tyrosinemia improve in the first year of life. We performed analyses of the HPD gene in a patient with tyrosinemia type III and two unrelated patients with hawkinsinuria. A homozygous missense mutation predicting an Ala to Val change at codon 268 (A268V) in the HPD gene was found in the patient with tyrosinemia type III. A heterozygous missense mutation predicting an Ala to Thr change at codon 33 (A33T) was found in the same HPD gene in the two patients with hawkinsinuria. These findings support the hypothesis that alterations in the structure and activity of HPD are causally related to two different metabolic disorders, tyrosinemia type III and hawkinsinuria.

  2. On the speed and acceleration of electron beams triggering interplanetary type III radio bursts

    CERN Document Server

    Krupar, Vratislav; Soucek, Jan; Santolik, Ondrej; Maksimovic, Milan; Kruparova, Oksana

    2015-01-01

    Type III radio bursts are intense radio emissions triggered by beams of energetic electrons often associated with solar flares. These exciter beams propagate outwards from the Sun along an open magnetic field line in the corona and in the interplanetary (IP) medium. We performed a statistical survey of 29 simple and isolated IP type III bursts observed by STEREO/Waves instruments between January 2013 and September 2014. We investigated their time-frequency profiles in order to derive the speed and acceleration of exciter electron beams. We show these beams noticeably decelerate in the IP medium. Obtained speeds range from $\\sim$ 0.02c up to $\\sim$ 0.35c depending on initial assumptions. It corresponds to electron energies between tens of eV and hundreds of keV, and in order to explain the characteristic energies or speeds of type III electrons ($\\sim 0.1$c) observed simultaneously with Langmuir waves at 1 au, the emission of type III bursts near the peak should be predominately at double plasma frequency. Der...

  3. Search for the Third Harmonic of Type III Bursts Radio Emission at Decameter Wavelengths

    Science.gov (United States)

    Brazhenko, A. I.; Melnik, V. N.; Konovalenko, A. A.; Pylaev, O. S.; Frantsuzenko, A. V.; Dorovskyy, V. V.; Vashchishin, R. V.; Rucker, H. O.

    The results of observations of trio bursts consisting of type III bursts are presented in this paper. The instantaneous frequency ratio of trio components is near 1:2:3. We analyze flow, duration, frequency drift rate and polarization of trio components as well as dependencies of these characteristics on frequency.

  4. Decameter Type III Bursts with Changing Frequency Drift-Rate Signs

    Science.gov (United States)

    Melnik, V. N.; Brazhenko, A. I.; Konovalenko, A. A.; Briand, C.; Dorovskyy, V. V.; Zarka, P.; Frantsuzenko, A. V.; Rucker, H. O.; Rutkevych, B. P.; Panchenko, M.; Denis, L.; Zaqarashvili, T.; Shergelashvili, B.

    2015-01-01

    We discuss properties of type III bursts that change the sign of their drift rate from negative to positive and vice versa. Moreover, these bursts may change the sign of their drift rates more than once. These particular type III bursts were observed simultaneously by the radio telescopes UTR-2 ( Ukrainian T-shaped Radio telescope, Kharkov, Ukraine), URAN-2 ( Ukrainian Radio telescope of the Academy of Sciences, Poltava, Ukraine), and by the NDA ( Nançay Decametric Array, Nancay, France) in the frequency range 8 - 41 MHz. The negative drift rates of these bursts are similar to those of previously reported decameter type III bursts and vary from -0.7 MHz s-1 to -1.7 MHz s-1, but their positive drift rates vary in a wider range from 0.44 MHz s-1 to 6 MHz s-1. Unlike inverted U-bursts, the tracks of these type III bursts have C- or inverted C-shapes.

  5. Aquatic Therapy for a Child with Type III Spinal Muscular Atrophy: A Case Report

    Science.gov (United States)

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-01-01

    Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons. This case report describes an aquatic therapy program and the outcomes for a 3-year-old girl with type III SMA. Motor skills were examined using the 88-item Gross Motor Function Measure (GMFM), the Peabody Developmental Motor Scales…

  6. MMP-12 catalytic domain recognizes and cleaves at multiple sites in human skin collagen type I and type III.

    Science.gov (United States)

    Taddese, Samuel; Jung, Michael C; Ihling, Christian; Heinz, Andrea; Neubert, Reinhard H H; Schmelzer, Christian E H

    2010-04-01

    Collagens of either soft connective or mineralized tissues are subject to continuous remodeling and turnover. Undesired cleavage can be the result of an imbalance between proteases and their inhibitors. Owing to their superhelical structure, collagens are resistant to many proteases and matrix metalloproteinases (MMPs) are required to initiate further degradation by other enzymes. Several MMPs are known to degrade collagens, but the action of MMP-12 has not yet been studied in detail. In this work, the potential of MMP-12 in recognizing sites in human skin collagen types I and III has been investigated. The catalytic domain of MMP-12 binds to the triple helix and cleaves the typical sites -Gly(775)-Leu(776)- in alpha-2 type I collagen and -Gly(775)-Ile(776)- in alpha-1 type I and type III collagens and at multiple other sites in both collagen types. Moreover, it was observed that the region around these typical sites contains comparatively less prolines, of which some have been proven to be only partially hydroxylated. This is of relevance since partial hydroxylation in the vicinity of a potential scissile bond may have a local effect on the conformational thermodynamics with probable consequences on the collagenolysis process. Taken together, the results of the present work confirm that the catalytic domain of MMP-12 alone binds and degrades collagens I and III. Copyright 2009 Elsevier B.V. All rights reserved.

  7. Structural characterization of CFA/III and Longus type IVb pili from enterotoxigenic Escherichia coli.

    Science.gov (United States)

    Kolappan, Subramaniapillai; Roos, Justin; Yuen, Alex S W; Pierce, Owen M; Craig, Lisa

    2012-05-01

    The type IV pili are helical filaments found on many Gram-negative pathogenic bacteria, with multiple diverse roles in pathogenesis, including microcolony formation, adhesion, and twitching motility. Many pathogenic enterotoxigenic Escherichia coli (ETEC) isolates express one of two type IV pili belonging to the type IVb subclass: CFA/III or Longus. Here we show a direct correlation between CFA/III expression and ETEC aggregation, suggesting that these pili, like the Vibrio cholerae toxin-coregulated pili (TCP), mediate microcolony formation. We report a 1.26-Å resolution crystal structure of CofA, the major pilin subunit from CFA/III. CofA is very similar in structure to V. cholerae TcpA but possesses a 10-amino-acid insertion that replaces part of the α2-helix with an irregular loop containing a 3(10)-helix. Homology modeling suggests a very similar structure for the Longus LngA pilin. A model for the CFA/III pilus filament was generated using the TCP electron microscopy reconstruction as a template. The unique 3(10)-helix insert fits perfectly within the gap between CofA globular domains. This insert, together with differences in surface-exposed residues, produces a filament that is smoother and more negatively charged than TCP. To explore the specificity of the type IV pilus assembly apparatus, CofA was expressed heterologously in V. cholerae by replacing the tcpA gene with that of cofA within the tcp operon. Although CofA was synthesized and processed by V. cholerae, no CFA/III filaments were detected, suggesting that the components of the type IVb pilus assembly system are highly specific to their pilin substrates.

  8. Disturbances in affective touch in hereditary sensory & autonomic neuropathy type III.

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Löken, Line; Axelrod, Felicia B; Kaufmann, Horacio

    2014-07-01

    Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1-10 cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.

  9. Alterations of thoraco-abdominal volumes and asynchronies in patients with spinal muscle atrophy type III.

    Science.gov (United States)

    LoMauro, Antonella; Romei, Marianna; Priori, Rita; Laviola, Marianna; D'Angelo, Maria Grazia; Aliverti, Andrea

    2014-06-15

    Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons resulting in muscle weakness. For the mild type III form, a sub-classification into type IIIA and IIIB, based on age of motor impairment, was recently proposed. To investigate if SMA IIIA (more severe) and IIIB differ also in terms of respiratory function, thoracoabdominal kinematics was measured during quiet breathing, inspiration preceding cough and inspiratory capacity on 5 type IIIA and 9 type IIIB patients. Four patients with SMA II (more severe than types III) and 19 healthy controls were also studied. Rib cage motion was similar in SMA IIIB and controls. Conversely, in SMA IIIA and SMA II it was significantly reduced and sometime paradoxical during quiet breathing in supine position. Our results suggest that in SMA IIIA intercostal muscles are weakened and the diaphragm is preserved similarly to SMA II, while in SMA IIIB the action of all inspiratory muscles is maintained. Sub-classification of type III seems feasible also for respiratory function.

  10. Vascular Ehlers-Danlos syndrome mutations in type III collagen differently stall the triple helical folding.

    Science.gov (United States)

    Mizuno, Kazunori; Boudko, Sergei; Engel, Jürgen; Bächinger, Hans Peter

    2013-06-28

    Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at a low temperature. At 33 °C, the natural collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at Gly-910 and at the C terminus at Gly-1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue.

  11. Polynomial Bundles and Generalised Fourier Transforms for Integrable Equations on A.III-type Symmetric Spaces

    Directory of Open Access Journals (Sweden)

    Vladimir S. Gerdjikov

    2011-10-01

    Full Text Available A special class of integrable nonlinear differential equations related to A.III-type symmetric spaces and having additional reductions are analyzed via the inverse scattering method (ISM. Using the dressing method we construct two classes of soliton solutions associated with the Lax operator. Next, by using the Wronskian relations, the mapping between the potential and the minimal sets of scattering data is constructed. Furthermore, completeness relations for the 'squared solutions' (generalized exponentials are derived. Next, expansions of the potential and its variation are obtained. This demonstrates that the interpretation of the inverse scattering method as a generalized Fourier transform holds true. Finally, the Hamiltonian structures of these generalized multi-component Heisenberg ferromagnetic (MHF type integrable models on A.III-type symmetric spaces are briefly analyzed.

  12. On the Energy Momentum in Bianchi Type I-III-V-VI0 Space-Time

    CERN Document Server

    Aygun, S; Tarhan, I; Aygun, Melis; Aygun, Sezgin; Tarhan, Ismail

    2006-01-01

    In this study, using the energy momentum definitions of Einstein, Moller, Bergmann-Thomson, Landau-Lifshitz and Papapetrou we compute the total energy-momentum distribution (due to matter and fields including gravitation) of the universe based on general Bianchi type I-III-V-VI(o) space-time and its transforms type I, III, V, VI(o) metrics, respectively. The energy-momentum densities are found exactly same for Einstein and Bergmann-Thomson definitions. The total energy and momentum is found to be zero for Bianchi types I and VI(o) space-times. These results are same as a previous works of Radinschi, Banerjee-Sen, Xulu and Aydogdu-Salti. Another point is that our study agree with previous works of Cooperstock-Israelit, Rosen, Johri et al.

  13. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. (Univ. of Southern California, Los Angeles (United States)); Murray, J. (Univ. of Iowa, Iowa City (United States)); Crall, M. (Ohio State Univ., Columbus (United States))

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  14. Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J;

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

  15. Salter-Harris type III fractures of the distal humerus in two dogs.

    Science.gov (United States)

    Hayes, G M; Radke, H; Langley-Hobbs, S J

    2011-01-01

    Salter-Harris type III fractures of the distal humerus in a four-month-old male Labrador Retriever and a male crossbreed dog (estimated to be 3.5-months-old) are reported. Both fractures were treated with open reduction and interfragmentary compression by lag screw fixation. Both fractures healed and full limb use was regained at four weeks postoperatively. The occurrence of this unusual fracture type may be related to the physeal closure pattern of the distal humeral physis, and a different mechanism of injury compared to the more common Salter-Harris type IV fracture seen in this region.

  16. Bianchi type-I, type-III and Kantowski-Sachs solutions in f( T) gravity

    Science.gov (United States)

    Rodrigues, M. E.; Kpadonou, A. V.; Rahaman, F.; Oliveira, P. J.; Houndjo, M. J. S.

    2015-06-01

    In the context of modified tele-parallel theory of gravity, we undertake cosmological anisotropic models and search for their solutions. Within a suitable choice of non-diagonal tetrads, the decoupled equations of motion are obtained for Bianchi-I, Bianchi-III and Kantowski-Sachs models, from which we obtain the correspondent solutions. By the way, energy density and pressures are also obtained, showing, as an important result, that our universe may live a quintessence like universe even while anisotropic models are considered.

  17. Esophagus or stomach? The seventh TNM classification for Siewert type II/III junctional adenocarcinoma.

    Science.gov (United States)

    Hasegawa, Shinichi; Yoshikawa, Takaki; Aoyama, Toru; Hayashi, Tsutomu; Yamada, Takanobu; Tsuchida, Kazuhito; Cho, Haruhiko; Oshima, Takashi; Yukawa, Norio; Rino, Yasushi; Masuda, Munetaka; Tsuburaya, Akira

    2013-03-01

    The aim of this study is to clarify whether TNM-EC or TNM-GC is better for classifying patients with AEG types II/III. The patients who had AEG types II/III and received D1 or more radical lymphadenectomy were selected. The patients were staged both by seventh edition of TNM-EC and TNM-GC. The distribution of the patients, the hazard ratio (HR) of each stage, and the separation of the survival were compared. A total of 163 patients were enrolled in this study. TNM-EC and TNM-GC classified 25 (20 and 5) and 32 (20 and 12) patients to stage I (IA and IB), 15 (4 and 11), and 33 (11 and 22) to stage II (IIA and IIB), 88 (24, 3, and 61) and 63 (14, 26, and 23) to stage III (IIIA, IIIB, and IIIC), and 35 and 35 to stage IV, respectively. The distribution of the patients was substantially deviated to stage IIIC in TNM-EC but was almost even in TNM-GC. A stepwise increase of HR was observed in TNM-GC, but not in TNM-EC. The survival curves between stages II and III were significantly separated in TNM-GC (P = 0.019), but not in TNM-EC (P = 0.204). The 5-year survival rates of stages IIIA, IIIB, and IIIC were 69.0, 100, and 38.9% in TNM-EC and were 52.0, 43.4, and 33.9% in TNM-GC, respectively. TNM-GC is better for classifying patients with AEG types II/III than TNM-EC is. These results could impact the next TNM revision for AEG.

  18. Dentin phosphoprotein compound mutation in dentin sialophosphoprotein causes dentinogenesis imperfecta type III.

    Science.gov (United States)

    Dong, Juan; Gu, TingTing; Jeffords, Leticia; MacDougall, Mary

    2005-01-30

    A rare compound mutation involving a 36 bp deletion and 18 bp insertion within exon 5 of the dentin sialophosphoprotein (DSPP) gene has been identified in a family with dentinogenesis imperfecta type III (DGI-III). The DSPP gene encodes two major tooth matrix proteins dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). DSPP mutations associated with DGI-III results in an in frame truncation of the serine aspartic acid triplet repeat found in DPP near the highly conserved carboxyl terminal region shortening the protein by six amino acids. Clinically this family presents with discolored amber opalescent teeth and severe attrition of the tooth structure. This study is the first report of a mutation within DPP associated with a genetic dentin disease. Our study indicates that DGI-III is allelic with some forms of DGI-II with and without progressive hearing loss and dentin dysplasia type II that have been shown to be caused by mutations within the DSP coding or signal peptide regions.

  19. A New Look at Type III Bursts and their Use as Coronal Diagnostics

    CERN Document Server

    Beltran, Samuel Tun; White, Stephen

    2015-01-01

    We present meter wave solar radio spectra of the highest spectrotemporal resolution achieved to date. The observations, obtained with the first station of the Long Wavelength Array (LWA1), show unprecedented detail of solar emissions across a wide bandwidth during a Type III/IIIb storm. Our flux calibration demonstrates that the LWA1 can detect Type III bursts much weaker than 1 SFU, much lower than previous observations, and that the distribution of fluxes in these bursts varies with frequency. The high sensitivity and low noise in the data provide strong constraints to models of this type of plasma emission. The continuous generation of electron beams in the corona revealed by the high density Type III storm is evidence for ubiquitous magnetic reconnection in the lower corona. Such an abundance of reconnection events not only contributes to the total coronal energy budget, but also provides an engine by which to form the populations of seed particles responsible for proton-rich solar energetic particle even...

  20. Hierarchical effector protein transport by the Salmonella Typhimurium SPI-1 type III secretion system.

    Directory of Open Access Journals (Sweden)

    Brit Winnen

    Full Text Available BACKGROUND: Type III secretion systems (TTSS are employed by numerous pathogenic and symbiotic bacteria to inject a cocktail of different "effector proteins" into host cells. These effectors subvert host cell signaling to establish symbiosis or disease. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the injection of SipA and SptP, two effector proteins of the invasion-associated Salmonella type III secretion system (TTSS-1. SipA and SptP trigger different host cell responses. SipA contributes to triggering actin rearrangements and invasion while SptP reverses the actin rearrangements after the invasion has been completed. Nevertheless, SipA and SptP were both pre-formed and stored in the bacterial cytosol before host cell encounter. By time lapse microscopy, we observed that SipA was injected earlier than SptP. Computer modeling revealed that two assumptions were sufficient to explain this injection hierarchy: a large number of SipA and SptP molecules compete for transport via a limiting number of TTSS; and the TTSS recognize SipA more efficiently than SptP. CONCLUSIONS/SIGNIFICANCE: This novel mechanism of hierarchical effector protein injection may serve to avoid functional interference between SipA and SptP. An injection hierarchy of this type may be of general importance, allowing bacteria to precisely time the host cell manipulation by type III effectors.

  1. In Situ Detection of Strong Langmuir Turbulence Processes in Solar Type III Radio Bursts

    Science.gov (United States)

    Golla, Thejappa; Macdowall, Robert J.; Bergamo, M.

    2012-01-01

    The high time resolution observations obtained by the WAVES experiment of the STEREO spacecraft in solar type III radio bursts show that Langmuir waves often occur as intense localized wave packets. These wave packets are characterized by short durations of only a few ms and peak intensities, which well exceed the supersonic modulational instability (MI) thresholds. These timescales and peak intensities satisfy the criterion of the solitons collapsed to spatial scales of a few hundred Debye lengths. The spectra of these wave packets consist of primary spectral peaks corresponding to beam-resonant Langmuir waves, two or more sidebands corresponding to down-shifted and up-shifted daughter Langmuir waves, and low frequency enhancements below a few hundred Hz corresponding to daughter ion sound waves. The frequencies and wave numbers of these spectral components satisfy the resonance conditions of the modulational instability (MI). Moreover, the tricoherences, computed using trispectral analysis techniques show that these spectral components are coupled to each other with a high degree of coherency as expected of the MI type of four wave interactions. The high intensities, short scale lengths, sideband spectral structures and low frequency spectral enhancements and, high levels of tricoherences amongst the spectral components of these wave packets provide unambiguous evidence for the supersonic MI and related strong turbulence processes in type III radio bursts. The implication of these observations include: (1) the MI and related strong turbulence processes often occur in type III source regions, (2) the strong turbulence processes probably play very important roles in beam stabilization as well as conversion of Langmuir waves into escaping radiation at the fundamental and second harmonic of the electron plasma frequency, fpe, and (3) the Langmuir collapse probably follows the route of MI in type III radio bursts.

  2. C1-C3 lateral mass fusion for type IIa and type III Hangman′s fracture

    Directory of Open Access Journals (Sweden)

    Natarajan Muthukumar

    2012-01-01

    Full Text Available Hangman′s fractures, also known as traumatic spondylolisthesis of axis, can be managed either conservatively with immobilization or by surgery. Surgery is usually indicated in cases with instability or failure of conservative treatment. Different surgical approaches, both anterior and posterior, have been described for treating Hangman′s fracture. We report two patients, one with type IIa and another with type III Hangman′s fracture treated with C1-C3 lateral mass fusion and discuss the advantages and limitations of this technique when compared to other techniques for fusion in patients with Hangman′s fracture.

  3. Type III Dyson Sphere of Highly Advanced Civilizations around a Super Massive Black Hole

    CERN Document Server

    Inoue, Makoto

    2011-01-01

    We describe a new system for a society of highly advanced civilizations around a super massive black hole (SMBH), as an advanced Type III "Dyson Sphere", pointing out an efficient usage of energy for the advanced civilizations. SMBH also works as a sink for waste materials. Here we assume that Type III civilisations of Kardashev classification [1] form a galactic club [2] in a galaxy, and the energy from the SMBH will be delivered to the club members, forming an energy control system similar to power grids in our present society. The energy is probably transmitted by a sharp beam with coherent electro-magnetic waves, which provide a new concept for the search for extraterrestrial intelligence (SETI) via detection of such energy transmission signals. This expands the search window for other intelligences within the Universe.

  4. New Tetrachromic VOF Stain (Type III-G.S for Normal and Pathological Fish Tissues

    Directory of Open Access Journals (Sweden)

    C Sarasquete

    2005-06-01

    Full Text Available A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus. In comparison to the original Gutiérrez´VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This facilitates the selective staining of different basic tissues and improves the morphological analysis of histochemical approaches of the cell components. The VOF-Type III G.S stain is composed of a mixture of several dyes of varying size and molecular weight (Orange G< acid Fuchsin< Light green

  5. Stacking fault domains as sources of a-type threading dislocations in III-nitride heterostructures

    Science.gov (United States)

    Smalc-Koziorowska, J.; Bazioti, C.; Albrecht, M.; Dimitrakopulos, G. P.

    2016-02-01

    A mechanism for the nucleation of a-type threading dislocation half-loops from basal stacking faults in wurtzite III-nitride heterostructures is presented. Transmission electron microscopy observations, in conjunction with topological and strain analysis, show that there are two possible configurations of closed domains comprising basal stacking faults of I1 type. It is shown that the lattice dislocation may emanate when the sphalerite structural units of the stacking faults in the closed domain are oriented in a parallel manner. The closed domain configurations do not introduce any shift on the basal planes, resulting in zero defect content along the growth direction. The stacking fault domains are hexagonal, with sides along the ⟨ 10 1 ¯ 0 ⟩ directions, and the threading dislocation half loops nucleate at the line nodes. The mechanism was found to be operational in multiple III-nitride systems.

  6. Type III events, flares and CMEs, in the extremely active period October-November 2003

    CERN Document Server

    Mitsakou, E; Preka-Papadema, P; Moussas, X; Hillaris, A; Caroubalos, C; Alissandrakis, C E; Tsitsipis, P; Kontogeorgos, A; Bougeret, J -L; Dumas, G; 10.1063/1.2347984

    2010-01-01

    The type III observations trace the propagation of energetic electron populations through the Solar Corona which, more often than not, precede or are associated with energy release on the Sun. A sample of Type III bursts in the range 20-650 MHz during the period of extraordinary solar activity (20 October to 4 November 2003) recorded by the ARTEMIS-IV1 radio spectrograph is analysed; its parameters are compared with characteristics of associated flares (Ha and GOES SXR) and CMEs, observed in the same period and reported in the SGR and the LASCO archives respectively. In this report we attempt to establish a correlation between energetic particles and major manifestations of solar activity such as flares and CMEs.

  7. RNA-activated DNA cleavage by the Type III-B CRISPR-Cas effector complex.

    Science.gov (United States)

    Estrella, Michael A; Kuo, Fang-Ting; Bailey, Scott

    2016-02-15

    The CRISPR (clustered regularly interspaced short palindromic repeat) system is an RNA-guided immune system that protects prokaryotes from invading genetic elements. This system represents an inheritable and adaptable immune system that is mediated by multisubunit effector complexes. In the Type III-B system, the Cmr effector complex has been found to cleave ssRNA in vitro. However, in vivo, it has been implicated in transcription-dependent DNA targeting. We show here that the Cmr complex from Thermotoga maritima can cleave an ssRNA target that is complementary to the CRISPR RNA. We also show that binding of a complementary ssRNA target activates an ssDNA-specific nuclease activity in the histidine-aspartate (HD) domain of the Cmr2 subunit of the complex. These data suggest a mechanism for transcription-coupled DNA targeting by the Cmr complex and provide a unifying mechanism for all Type III systems.

  8. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.

    Science.gov (United States)

    Rüetschi, U; Cerone, R; Pérez-Cerda, C; Schiaffino, M C; Standing, S; Ugarte, M; Holme, E

    2000-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.

  9. Stopping Frequency of Type III Solar Radio Bursts in Expanding Magnetic Flux Tubes

    CERN Document Server

    Reid, Hamish A S

    2015-01-01

    Understanding the properties of type III radio bursts in the solar corona and interplanetary space is one of the best ways to remotely deduce the characteristics of solar accelerated electron beams and the solar wind plasma. One feature of all type III bursts is the lowest frequency they reach (or stopping frequency). This feature reflects the distance from the Sun that an electron beam can drive the observable plasma emission mechanism. The stopping frequency has never been systematically studied before from a theoretical perspective. Using numerical kinetic simulations, we explore the different parameters that dictate how far an electron beam can travel before it stops inducing a significant level of Langmuir waves, responsible for plasma radio emission. We use the quasilinear approach to model self-consistently the resonant interaction between electrons and Langmuir waves in inhomogeneous plasma, and take into consideration the expansion of the guiding magnetic flux tube and the turbulent density of the in...

  10. Clumpy Langmuir waves in type III radio sources - Comparison of stochastic-growth theory with observations

    Science.gov (United States)

    Robinson, P. A.; Cairns, I. H.; Gurnett, D. A.

    1993-01-01

    Detailed comparisons are made between the Langmuir-wave properties predicted by the recently developed stochastic-growth theory of type III sources and those observed by the plasma wave experiment on ISEE 3, after correcting for the main instrumental and selection effects. Analysis of the observed field-strength distribution confirms the theoretically predicted form and implies that wave growth fluctuates both spatially and temporally in sign and magnitude, leading to an extremely clumpy distribution of fields. A cutoff in the field-strength distribution is seen at a few mV/m, corresponding to saturation via nonlinear effects. Analysis of the size distribution of Langmuir clumps yields results in accord with those obtained in earlier work and with the size distribution of ambient density fluctuations in the solar wind. This confirms that the inhomogeneities in the Langmuir growth rate are determined by the density fluctuations and that these fluctuations persist during type III events.

  11. Propagation of energetic electrons from the corona into interplanetary space and type III radio emission

    CERN Document Server

    Breitling, F; Vocks, C

    2015-01-01

    During solar flares a large amount of electrons with energies greater than 20 keV is generated with a production rate of typically $10^{36}$ s$^{-1}$. A part of them is able to propagate along open magnetic field lines through the corona into interplanetary space. During their travel they emit radio radiation which is observed as type III radio bursts in the frequency range from 100 MHz down to 10 kHz by the WAVES radio spectrometer aboard the spacecraft WIND, for instance. From the drift rates of these bursts in dynamic radio spectra the radial propagation velocity $V_r$ of the type III burst exciting electrons is derived by employing a newly developed density model of the heliosphere. Calculations show that the radio radiation is emitted by electrons with different $V_r$ and therefore by different electrons of the initially produced electron distribution.

  12. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed [Mansoura Faculty of Medicine, Department of Diagnostic Radiology, Mansoura (Egypt); Abdalla, Ahmed; Fathy, Abeer [Mansoura Faculty of Medicine, Department of Pediatric, Mansoura (Egypt); Azab, Ahmed [Mansoura Faculty of Medicine, Department of Neurology, Mansoura (Egypt); Rahman, Ashraf Abdel [Radiology Unit of Pediatric Hospital, Mansoura (Egypt)

    2009-11-15

    The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm{sup 2} was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

  13. Type III Seesaw and Dark Matter in a Supersymmetric Left-Right Model

    CERN Document Server

    Borah, Debasish

    2009-01-01

    We propose a new supersymmetric left right model with Higgs doublets carrying odd B-L charge, higgs bidoublet and heavy Higgs triplets with zero B-L charge and a set of sterile neutrinos which are singlet under the gauge group. We show that spontaneous parity violation can be achieved naturally in this model and the neutrino masses arise from the so called type III seesaw mechanism. We also discuss the possible phenomenology in the context of neutrino masses and dark matter.

  14. Global Analysis of a Delayed Impulsive Lotka-Volterra Model with Holling III Type Functional Response

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2015-01-01

    Full Text Available A delayed impulsive Lotka-Volterra model with Holing III type functional response was established. With the help of Mawhin’s Continuation Theorem in coincidence degree theory, a sufficient condition is found for the existence of positive periodic solutions of the system under consideration. By applying the comparison theorem and constructing a suitable Lyapunov functional, the permanence and global attractivity of the model are proved. Two numerical simulations are also given to illustrate our main results.

  15. Anisotropic Dark Energy Bianchi Type III Cosmological Models in Brans Dicke Theory of Gravity

    CERN Document Server

    Shamir, M Farasat; 10.1139/P2012-007

    2012-01-01

    The main purpose of this paper is to explore the solutions of Bianchi type $III$ cosmological model in Brans Dicke theory of gravity in the background of anisotropic dark energy. We use the assumption of constant deceleration parameter and power law relation between scalar field $\\phi$ and scale factor $a$ to find the solutions. The physical behavior of the solutions has been discussed using some physical quantities.

  16. Infection Reduces Return-to-duty Rates for Soldiers with Type III Open Tibia Fractures

    Science.gov (United States)

    2014-09-01

    Type III open tibia fracture and tabulated the prevalence of infectious complications.We searched the Physical Evaluation Board database to determine...disability among combat casualties, with an average disability rating of 42% based on the Physical Evaluation Board.8 In addition, it has been...redness, warmth , swelling, or purulence that required operative inter- vention. Osteomyelitis was defined as deep infection with positive bone cultures

  17. Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III.

    Science.gov (United States)

    D'Eufemia, Patrizia; Finocchiaro, Roberto; Celli, Mauro; Raccio, Ivana; Properzi, Enrico; Zicari, Alessandra

    2009-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPD). Few cases have been described with mental retardation or neurological symptoms. Recently it has been demonstrated that 4-HPD participates to nitric oxide (NO) intracellular sequestration in Pseudomonas aeruginosa. 4-HPD is an ubiquitous enzyme with a prominent expression in neutrophils and neurons. In the nervous system NO has been perceived to be a potential neuromodulator although prolonged excessive generation is detrimental. We analyzed NO release by neutrophils of a patient with tyrosinemia type III in order to evaluate a possible influence of 4-HPD deficiency on this process. Our patient, previously described, is a 30-year-old women with persistent tyrosinemia (450-680 micromol/l) and deficient activity of 4-HPD. At 17 months of age she experienced an acute ataxia and drowsiness lasting for 10 days, but further clinical course showed persistent tyrosinemia with normal growth and psychomotor development. Neutrophils isolated from our patient exhibited a NO release greatly higher in respect to the controls (mean+/-SEM 23.2+/-1.8 micromol/10(6) cells vs 3.5+/-0.5 micromol/10(6) cells). Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation but no consistent phenotype has emerged. Therefore the pathogenesis of neurological involvement is yet not well understood. Our results suggest that an excessive neutrophils of NO release could reflect the lack of scavenging action of 4-HPD. Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III.

  18. Observation of Current Structures at Type-III ELM Onset on EAST

    DEFF Research Database (Denmark)

    Yan, Ning; Naulin, Volker; Xu, G.

    In far scrape-o layer (SOL), alternating negative and positive burst structures in ion saturation current were detected at the onset of each type-III edge localized mode (ELM) on EAST. Different from the fast streaming phenomenon reported previously, one subsequent positive burst structure appears...... led generated by scrape-off layer current can ultimately trigger the ELM through the coupling with MHD modes inside the separatrix....

  19. Observation of local radio emission associated with type III radio bursts and Langmuir waves

    Science.gov (United States)

    Reiner, M. J.; Stone, R. G.; Fainberg, J.

    1992-01-01

    The first clear detection of fundamental and harmonic radiation from the type III radio source region is presented. This radiation is characterized by its lack of frequency drift, its short rise and decay times, its relative weakness compared to the remotely observed radiation and its temporal coincidence with observed Langmuir waves. The observations were made with the radio and plasma frequency (URAP) receivers on the Ulysses spacecraft between about 1 and 2 AU from the Sun.

  20. Searching the charged Higgs boson of the type III two Higss doublet model

    CERN Document Server

    Cardenas, H

    2008-01-01

    In the framework of the Two Higgs Doublet Model (2HDM) type III appears two charged Higgs boson and recently there are experimental reports from D0 and CDF collaborations searching a particular signature of new physics. We present a review of the analisys done in the region $M_{H^+}>m_t$ by D0 collaboration and we use the ratio $R_\\sigma$ for the region $M_{H^+} < m_t$ in different scenarios of space parameter of this model.

  1. Prediction of type III secretion signals in genomes of gram-negative bacteria.

    Directory of Open Access Journals (Sweden)

    Martin Löwer

    Full Text Available BACKGROUND: Pathogenic bacteria infecting both animals as well as plants use various mechanisms to transport virulence factors across their cell membranes and channel these proteins into the infected host cell. The type III secretion system represents such a mechanism. Proteins transported via this pathway ("effector proteins" have to be distinguished from all other proteins that are not exported from the bacterial cell. Although a special targeting signal at the N-terminal end of effector proteins has been proposed in literature its exact characteristics remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that the signals encoded in the sequences of type III secretion system effectors can be consistently recognized and predicted by machine learning techniques. Known protein effectors were compiled from the literature and sequence databases, and served as training data for artificial neural networks and support vector machine classifiers. Common sequence features were most pronounced in the first 30 amino acids of the effector sequences. Classification accuracy yielded a cross-validated Matthews correlation of 0.63 and allowed for genome-wide prediction of potential type III secretion system effectors in 705 proteobacterial genomes (12% predicted candidates protein, their chromosomes (11% and plasmids (13%, as well as 213 Firmicute genomes (7%. CONCLUSIONS/SIGNIFICANCE: We present a signal prediction method together with comprehensive survey of potential type III secretion system effectors extracted from 918 published bacterial genomes. Our study demonstrates that the analyzed signal features are common across a wide range of species, and provides a substantial basis for the identification of exported pathogenic proteins as targets for future therapeutic intervention. The prediction software is publicly accessible from our web server (www.modlab.org.

  2. Identification, Characterization, and Developmental Expression Pattern of Type III Interferon Receptor Gene in the Chinese Goose

    Directory of Open Access Journals (Sweden)

    Qin Zhou

    2015-01-01

    Full Text Available Interferons, as the first line of defense against the viral infection, play an important role in innate immune responses. Type III interferon (IFN-λ was a newly identified member of IFN family, which plays IFN-like antiviral activity. Towards a better understanding of the type III interferon system in birds, type III interferon lambda receptor (IFNLR1 was first identified in the Chinese goose. In this paper, we had cloned 1952 bp for goose IFNLR1 (goIFNLR1, including an ORF of 1539 bp, encoding a 512-amino acid protein with a 20 aa predict signal peptide at its N terminal and a 23 aa transmembrane region. The predicted amino acid sequence of goIFNLR1 has 90%, 73%, and 34% identity with duck IFNLR1 (predicted sequence, chicken IFNLR1, and human IFNLR1, respectively. And the age-related tissue distribution of goIFNLR1 was identified by Real Time quantitative PCR (RT-qPCR, we found that the goIFNLR1 has a mainly expression in epithelium-rich tissues similar to other species’, such as small intestinal, lung, liver, and stomach. Moreover, a relatively high expression of goIFNLR1 was also observed in the secondary immune tissues (harderian gland and cecal tonsil. The identification and tissue distribution of goIFNLR1 will facilitate further study of the role of IFN-λ in goose antiviral defense.

  3. The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

    Directory of Open Access Journals (Sweden)

    Vestri Anna R

    2009-12-01

    Full Text Available Abstract Background This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects. Methods The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ. One-hundred healthy volunteers were recruited as a control group. Results The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result and 2.2% in the control group (p Conclusions Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis.

  4. Functional relatedness in the Inv/Mxi-Spa type III secretion system family.

    Science.gov (United States)

    Klein, Jessica A; Dave, Biren M; Raphenya, Amogelang R; McArthur, Andrew G; Knodler, Leigh A

    2017-03-01

    Type III Secretion Systems (T3SSs) are structurally conserved nanomachines that span the inner and outer bacterial membranes, and via a protruding needle complex contact host cell membranes and deliver type III effector proteins. T3SS are phylogenetically divided into several families based on structural basal body components. Here we have studied the evolutionary and functional conservation of four T3SS proteins from the Inv/Mxi-Spa family: a cytosolic chaperone, two hydrophobic translocators that form a plasma membrane-integral pore, and the hydrophilic 'tip complex' translocator that connects the T3SS needle to the translocon pore. Salmonella enterica serovar Typhimurium (S. Typhimurium), a common cause of food-borne gastroenteritis, possesses two T3SSs, one belonging to the Inv/Mxi-Spa family. We used invasion-deficient S. Typhimurium mutants as surrogates for expression of translocator orthologs identified from an extensive phylogenetic analysis, and type III effector translocation and host cell invasion as a readout for complementation efficiency, and identified several Inv/Mxi-Spa orthologs that can functionally substitute for the S. Typhimurium chaperone and translocator proteins. Functional complementation correlates with amino acid sequence identity between orthologs, but varies considerably between the four proteins. This is the first in-depth survey of the functional interchangeability of Inv/Mxi-Spa T3SS proteins acting directly at the host-pathogen interface. © 2016 John Wiley & Sons Ltd.

  5. Evidence for Langmuir Envelope Solitons in Solar Type III Burst Source Regions

    Science.gov (United States)

    Thejappa, G.; Goldstein, M. L.; MacDowall, R. J.; Papadopoulos, K.; Stone, R. G.

    1998-01-01

    We present observational evidence for the generation of Langmuir envelope solitons in the source regions of solar type III radio bursts. The solitons appear to be formed by electron beams which excite either the modulational instability or oscillating two-stream instability (OTSI). Millisecond data from the Ulysses Unified Radio and Plasma Wave Experiment (URAP) show that Langmuir waves associated with type III bursts occur as broad intense peaks with time scales ranging from 15 to 90 milliseconds (6 - 27 km). These broad field structures have the properties expected of Langmuir envelope solitons, viz.: the normalized peak energy densities, W(sub L)/n(sub e)T(sub e) approximately 10(exp -5), are well above the modulational instability threshold; the spatial scales, L, which range from 1 - 5 Langmuir wavelengths, show a high degree of inverse correlation with (W(sub L)/n(sub e)T(sub e))(sup 1/2); and the observed widths of these broad peaks agree well with the predicted widths of envelope solitons. We show that the orientation of the Langmuir field structures is random with respect to the ambient magnetic field, indicating that they are probably isotropic structures that have evolved from initially pancake-like solitons. These observations suggest that strong turbulence processes, such as the modulational instability or the OTSI, stabilize the electron beams that produce type III bursts.

  6. [Triple-Endobutton technique for the treatment of Tossy type III acromioclavicular joint dislocation].

    Science.gov (United States)

    Sun, Liao-jun; Lu, Di; Chen, Hua

    2015-06-01

    To evaluate the clinical outcomes and complications of Triple-Endobutton plates in treating Tossy type III acromioclavicular joint dislocation. From January 2011 to January 2013,45 patients with Tossy type III acromioclavicular joint dislocation were treated with Triple-Endobutton plates. There were 35 males and 10 females with an average age of 30.5 (ranged from 19 to 60) years old. At the final follow-up, VAS, DASH, Constant-Murley criterion were used to evaluate shoulder function. All patients were followed up from 15 to 36 months. No neurovascular injury, wound infection and stress fractures were found,but 3 patients had a re-dislocation. At the final follow-up,the mean VAS score was decreased from (5.7±1.6) preoperatively to postoperative (0.2±0.1); DASH score was significantly decreased from (19.6±4.3) preoperatively to (0.3±0.1) postoperatively; Constant-Murley score was improved from (34.4±4.3) before operation to (94.8± 3.5) after operation. Clinical outcomes of treating Tossy type III acromioclavicular joint dislocation with Triple-Endobutton plates is satisfactory. However, re-dislocation is still the most common complication. Careful perioperative management is an important factor in preventing re-dislocation.

  7. Operated DeBakey type III dissecting aortic aneurysm: review of 12 cases

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Hi Eun; Lee, Ghi Jai; Oh, Sang Joon; Yoon, Sei Ra; Shim, Jae Chan; Kim, Ho Kyun; Han, Chang Yul [Inje University, Seoul Paik Hospital, Seoul (Korea, Republic of)

    1995-06-15

    We evaluated the indications of operation and radiologic findings in 12 operated DeBakey type III aortic dissections. We retrospectively reviewed radiologic findings of 12 operated DeBakey type III aortic dissections, using CT, MRI, or aortography, and correlations were made with clinical course of the patients. Three cases were uncomplicated dissections. There were aneurysm rupture in 4 cases, impending rupture in 4 cases, occlusion of common iliac artery in 2 cases, occlusion of renal artery in 1 case, and compression of bronchus and esophagus by dilated aorta in 1 case. Associated clinical sign and symptoms were chest and back pain in 12 cases, claudication in 3 cases, dyspnea and dysphagia in 1 case, hoarseness in 1 case, and hemoptysis in 1 case. Post-operative complications were death from aneurysm rupture in 1 case, paraplegia in 2 cases, acute renal failure in 3 cases, and hemopericardium in 1 case. Although medical therapy is preferred in management of DeBakey type III aortic dissection, surgical treatment should be considered in patients with radiological findings of aortic rupture, impending rupture, occlusion of aortic major branches.

  8. HVEM serial-section analysis of rabbit foliate taste buds: I. Type III cells and their synapses.

    Science.gov (United States)

    Royer, S M; Kinnamon, J C

    1991-04-01

    Serially sectioned rabbit foliate taste buds were examined with high voltage electron microscopy (HVEM) and computer-assisted, three-dimensional reconstruction. This report focuses on the ultrastructure of the type III cells and their synapses with sensory nerve fibers. Type III cells have previously been proposed to be the primary gustatory receptor cells in taste buds of rabbits and other mammals. Within rabbit foliate taste buds, type III cells constitute a well-defined, easily recognizable class and are the only taste bud cells observed to form synapses with intragemmal nerve fibers. Among 18 type III cells reconstructed from serial sections, 11 formed from 1 to 6 synapses each with nerve fibers; 7 reconstructed type III cells formed no synapses. Examples of both convergence and divergence of synaptic input from type III cells onto nerve fibers were observed. The sizes of the active zones of the synapses and numbers of vesicles associated with the presynaptic membrane specializations were highly variable. Dense-cored vesicles 80-140 nm in diameter were often found among the 40-60 nm clear vesicles clustered at presynaptic sites. At some synapses, these large dense-cored vesicles appeared to be the predominant vesicle type. This observation suggests that there may be functionally different types of synapses in taste buds, distinguished by the prevalence of either clear or dense-cored vesicles. Previous investigations have indicated that the dense-cored vesicles in type III cells may be storage sites for biogenic amines.

  9. Results of Operative and Nonoperative Treatment of Rockwood Types III and V Acromioclavicular Joint Dislocation

    Science.gov (United States)

    Joukainen, Antti; Kröger, Heikki; Niemitukia, Lea; Mäkelä, E. Antero; Väätäinen, Urho

    2014-01-01

    Background: The optimal treatment of acute, complete dislocation of the acromioclavicular joint (ACJ) is still unresolved. Purpose: To determine the difference between operative and nonoperative treatment in acute Rockwood types III and V ACJ dislocation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: In the operative treatment group, the ACJ was reduced and fixed with 2 transarticular Kirschner wires and ACJ ligament suturing. The Kirschner wires were extracted after 6 weeks. Nonoperatively treated patients received a reduction splint for 4 weeks. At the 18- to 20-year follow-up, the Constant, University of California at Los Angeles Shoulder Rating Scale (UCLA), Larsen, and Simple Shoulder Test (SST) scores were obtained, and clinical and radiographic examinations of both shoulders were performed. Results: Twenty-five of 35 potential patients were examined at the 18- to 20-year follow-up. There were 11 patients with Rockwood type III and 14 with type V dislocations. Delayed surgical treatment for ACJ was used in 2 patients during follow-up: 1 in the operatively treated group and 1 in the nonoperatively treated group. Clinically, ACJs were statistically significantly less prominent or unstable in the operative group than in the nonoperative group (normal/prominent/unstable: 9/4/3 and 0/6/3, respectively; P = .02) and in the operative type III (P = .03) but not type V dislocation groups. In operatively and nonoperatively treated patients, the mean Constant scores were 83 and 85, UCLA scores 25 and 27, Larsen scores 11 and 11, and SST scores 11 and 12 at follow-up, respectively. There were no statistically significant differences in type III and type V dislocations. In the radiographic analysis, the ACJ was wider in the nonoperative than the operative group (8.3 vs 3.4 mm; P = .004), and in the type V dislocations (nonoperative vs operative: 8.5 vs 2.4 mm; P = .007). There was no statistically significant difference between study groups in

  10. Characteristic Relations of Type-III Intermittency in an Electronic Circuit

    CERN Document Server

    Kim, C M; Ryu, J W; Park, Y J; Kim, Chil-Min; Yim, Geo-Su; Ryu, Jung-Wan; Park, Young-Jai

    1998-01-01

    It is reported that the characteristic relations of type-II and type-III intermittencies, with respective local Poincar$\\acute{e}$ maps of $x_{n+1}= (1+\\epsilon)x_n + a x^3_n$ and $x_{n+1}= - (1+\\epsilon)x_n - a x^3_n$, are both $- ln (\\epsilon)$ under the assumption of uniform reinjection probability. However, the intermittencies have various characteristic relations such as probability. In this Letters the various characteristic relations are discussed, and the $\\epsilon^{-1/2}$ characteristic relation is obtained experimentally in an electronic circuit, with uniform reinjection probability.

  11. First report on methicillin-resistant Staphylococcus aureus of Spa type T037, Sequence type 239, SCCmec type III/IIIA in Malaysia

    NARCIS (Netherlands)

    V. Neela (Vasanthakumari); H. Ghasemzadeh Moghaddam (Hamed); A.F. van Belkum (Alex); D. Horst-Kreft (Deborah); N.S. Mariana (Nor Shamsudin); E. Ghaznavi Rad (Ehsanollah)

    2010-01-01

    textabstractMethicillin-resistant Staphylococcus aureus (MRSA) from Malaysia were shown to possess staphylococcal cassette chromosome mec (SCCmec)-III and IIIA. Spa sequencing and multi-locus sequence typing (MLST) documented t037 and ST 239 (CC8) for 83.3% of the isolates. This confirms

  12. Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review.

    Science.gov (United States)

    Wolfenden, C; Wittkowski, A; Hare, D J

    2017-08-30

    The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.

  13. Biological effects of chicken type III interferon on expression of interferon-stimulated genes in chickens: comparison with type I and type II interferons.

    Science.gov (United States)

    Masuda, Yasumitsu; Matsuda, Akiko; Usui, Tatsufumi; Sugai, Toru; Asano, Atsushi; Yamano, Yoshiaki

    2012-11-01

    Interferons (IFNs) are key mediators that activate host defense mechanisms against viruses. The recently identified mammalian Type III IFN has biological effects similar to type I IFN. However, the biological effects of type III IFN have not yet been characterized in birds. We compared the effects of chicken type III IFN (IFN-λ) with type I (IFN-β) and type II (IFN-γ) IFNs on IFN-stimulated genes (ISGs) using recombinant proteins expressed in Escherichia coli. Recombinant chicken IFN-λ inhibited influenza virus replication and induced the mRNA expression of the ISGs, Mx and OAS, in chicken embryonic fibroblasts (CEFs) in a dose-dependent manner. However, the effective dose of IFN-λ was higher than that of IFN-β and IFN-γ. Furthermore, the effect of IFN-λ on induction of Mx and OAS was lesser than that of IFN-β, but comparable to that of IFN-γ. These results indicate that chicken IFN-λ has the potential to induce ISGs and inhibit viral replication in chicken cells.

  14. Expression and Quorum Sensing Regulation of Type III Secretion System Genes of Vibrio harveyi during Infection of Gnotobiotic Brine Shrimp.

    Science.gov (United States)

    Ruwandeepika, H A Darshanee; Karunasagar, Indrani; Bossier, Peter; Defoirdt, Tom

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells.

  15. SORPTION OF Ga (III ON FLEXIBLE OPEN CELL POLYURETHANE FOAM OF POLYETHER TYPE IMPREGNATED WITH TRI-N-BUTHYL PHOSPATE

    Directory of Open Access Journals (Sweden)

    Lavinia Tofan

    2007-06-01

    Full Text Available The obtained results concerning the Ga (III ion retention on flexible open cell polyurethane foam of polyether type pretreated with tri-n-butyl phosphate are presented. The influence of solution acidity, phases contact time, Ga (III concentration and solution temperature have been investigated. The parameters of Ga (III batch sorption have been optimized. On the basis of Langmuir isotherms, the sorption constants and the thermodynamic parameters, ∆G, ∆Η and ∆S have been calculated.

  16. Salter-Harris type III fractures of the distal femur: plain radiographs can be deceptive.

    Science.gov (United States)

    Lippert, William C; Owens, Richard F; Wall, Eric J

    2010-09-01

    Salter-Harris (SH) III fractures of the distal femur, although rare, can have devastating effects. The purposes of this study were to: (1) compare the intra-articular fracture displacement measured on plain x-ray and magnetic resonance imaging (MRI) or computed tomography (CT) scan and (2) report the outcomes of patients with a SH III fracture of the distal femur. All SH III distal femur fractures treated at a large Children's Hospital with a Level I Pediatric Trauma Center between 1995 and 2006 were retrospectively reviewed. A total of 14 patients (average age: 13 y, 11 mo; range: 7 y, 8 mo to 17 y, 11 mo) with an average follow-up time of 21.50 months (range: 2 to 47 mo) were included in this study. Fracture displacement on plain x-ray was compared with the fracture displacement measured on MRI or CT scan. The average time between the initial plain x-ray and MRI or CT scan was 37.48 days (range: 3 h to 6 mo). Plain x-rays significantly underestimated the displacement of SH III fractures versus MRI or CT scan. Six patients who had both plain x-ray and MRI or CT scan had a measured displacement of 0.42 mm and 2.70 mm, respectively (paired Student t test, P=0.005). Ten of the 14 patients (71%) had no physical limitations and full knee motion at their most recent follow-up visit. The treatment of 4 patients (29%) was changed based on the findings of the additional MRI or CT scan. This study and earlier studies have shown a high rate of poor results with SH III fractures of the distal femur. This type of fracture pattern is extremely unstable and the true displacement is often underestimated by x-rays. Thus, it is strongly recommended that an MRI or CT scan be obtained on every SH III fracture of the distal femur. Moreover, any SH III fracture visible on plain radiographs should be treated with open reduction, internal fixation. Level IV.

  17. NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives.

    Science.gov (United States)

    Brisson, J R; Uhrinova, S; Woods, R J; van der Zwan, M; Jarrell, H C; Paoletti, L C; Kasper, D L; Jennings, H J

    1997-03-18

    The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

  18. Epigenetic reprogramming of the type III interferon response potentiates antiviral activity and suppresses tumor growth.

    Directory of Open Access Journals (Sweden)

    Siyuan Ding

    2014-01-01

    Full Text Available Type III interferon (IFN-λ exhibits potent antiviral activity similar to IFN-α/β, but in contrast to the ubiquitous expression of the IFN-α/β receptor, the IFN-λ receptor is restricted to cells of epithelial origin. Despite the importance of IFN-λ in tissue-specific antiviral immunity, the molecular mechanisms responsible for this confined receptor expression remain elusive. Here, we demonstrate that the histone deacetylase (HDAC repression machinery mediates transcriptional silencing of the unique IFN-λ receptor subunit (IFNLR1 in a cell-type-specific manner. Importantly, HDAC inhibitors elevate receptor expression and restore sensitivity to IFN-λ in previously nonresponsive cells, thereby enhancing protection against viral pathogens. In addition, blocking HDAC activity renders nonresponsive cell types susceptible to the pro-apoptotic activity of IFN-λ, revealing the combination of HDAC inhibitors and IFN-λ to be a potential antitumor strategy. These results demonstrate that the type III IFN response may be therapeutically harnessed by epigenetic rewiring of the IFN-λ receptor expression program.

  19. Management of Oehler’s Type III Dens Invaginatus Using Cone Beam Computed Tomography

    Directory of Open Access Journals (Sweden)

    Jaya Ranganathan

    2016-01-01

    Full Text Available Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler’s classification (1957 for Dens Invaginatus (DI into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler’s Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation.

  20. Decreased type III collagen expression in human uterine cervix of prolapse uteri

    Science.gov (United States)

    IWAHASHI, MASAAKI; MURAGAKI, YASUTERU

    2011-01-01

    The precise mechanism of prolapse uteri is not fully understood. There is evidence to suggest that abnormalities of collagen, the main component of extracellular matrix, or its repair mechanism, may predispose women to prolapse. To investigate the characteristic structure of human uterine cervix of patients with prolapse uteri, various types of collagen expression in the uterine cervix tissues of the prolapse uteri were compared to those of normal uterine cervix. After informed consent, 36 specimens of uterine cervical tissues were obtained at the time of surgery from 16 postmenopausal women with prolapse uteri (stage III–IV by the Pelvic Organ Prolapse Quantification examination) and 20 postmenopausal women without prolapse uteri (control group). Collagens were extracted from the uterine cervix tissues by salt precipitation methods. The relative levels of various collagens were evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The uterine cervix was longer in the patients with prolapse uteri than those of postmenopausal controls without prolapse uteri. The ratios of type III to type I collagen in the uterine cervical tissues were significantly decreased in the prolapse uteri, as compared to those of the postmenopausal uterine cervix without prolapse. These results suggest that decreased type III collagen expression may play an important role in determing the physiology and structure of the uterine cervix tissues of prolapse uteri. PMID:22977496

  1. Analysis of the characteristics of patients with open tibial fractures of Gustilo and Anderson type III

    Directory of Open Access Journals (Sweden)

    Frederico Carlos Jaña Neto

    2016-04-01

    Full Text Available OBJECTIVE: To analyze the characteristics of patients with Gustilo-Anderson Type III open tibial fractures treated at a tertiary care hospital in São Paulo between January 2013 and August 2014. METHODS: This was a cross-sectional retrospective study. The following data were gathered from the electronic medical records: age; gender; diagnosis; trauma mechanism; comorbidities; associated fractures; Gustilo and Anderson, Tscherne and AO classifications; treatment (initial and definitive; presence of compartment syndrome; primary and secondary amputations; MESS (Mangled Extremity Severity Score index; mortality rate; and infection rate. RESULTS: 116 patients were included: 81% with fracture type IIIA, 12% IIIB and 7% IIIC; 85% males; mean age 32.3 years; and 57% victims of motorcycle accidents. Tibial shaft fractures were significantly more prevalent (67%. Eight patients were subjected to amputation: one primary case and seven secondary cases. Types IIIC (75% and IIIB (25% predominated among the patients subjected to secondary amputation. The MESS index was greater than 7 in 88% of the amputees and in 5% of the limb salvage group. CONCLUSION: The profile of patients with open tibial fracture of Gustilo and Anderson Type III mainly involved young male individuals who were victims of motorcycle accidents. The tibial shaft was the segment most affected. Only 7% of the patients underwent amputation. Given the current controversy in the literature about amputation or salvage of severely injured lower limbs, it becomes necessary to carry out prospective studies to support clinical decisions.

  2. Type III Supracondylar Humerus Fractures in Children: Open Reduction and Pinning

    Directory of Open Access Journals (Sweden)

    Firat Ozan

    2016-04-01

    Full Text Available Aim: Supracondylar humerus fractures are the most common type of fractures involving the elbow region in children. Open reduction is a successful method for the management of displaced supracondylar fractures, with the most important advantages being complete anatomical reduction by visualising the fracture line and the lower level of risk for iatrogenic neurovascular injuries. In the present study, we assessed outcomes of open reduction and cross-pinning employed in the surgical management of paediatric Gartland type III supracondylar humerus fractures. Material and Method: The study included 18 children with Gartland extension type III supracondylar humerus fractures (13 boys, 5 girls; mean age: 7.3 ± 2.02 years; range, 3%u201312. There were fractures in the right elbows of 11 patients (61.1% and in the left elbows of seven (38.8%. The mean operative time was 53.3 ± 8.5 minutes (range, 45%u201370. The mean length of hospital stay was 1.7 ± 0.75 days (range, 1%u20133, while the mean follow-up time was 2.2 ± 0.6 years (range, 1.5%u20134. Results: According to the Flynn criteria, excellent results were obtained in six patients (33.3%, and good results in 12 (61.7% regarding changes in the carrying angle of the elbow. Functional assessment results were excellent for 14 patients (77.7% and good for four (22.3% regarding their loss of joint movement. Radiographic examinations revealed an average Baumann%u2019s angle of 75.6° (range, 70%u201385. Discussion: Good clinical outcomes can be achieved through the management of Gartland extension type III supracondylar humerus fractures using the open reduction technique. The most important disadvantage, however, is the post-surgical appearance of the elbow incision scar.

  3. The type III secreted protein BspR regulates the virulence genes in Bordetella bronchiseptica.

    Directory of Open Access Journals (Sweden)

    Jun Kurushima

    Full Text Available Bordetella bronchiseptica is closely related with B. pertussis and B. parapertussis, the causative agents of whooping cough. These pathogenic species share a number of virulence genes, including the gene locus for the type III secretion system (T3SS that delivers effector proteins. To identify unknown type III effectors in Bordetella, secreted proteins in the bacterial culture supernatants of wild-type B. bronchiseptica and an isogenic T3SS-deficient mutant were compared with iTRAQ-based, quantitative proteomic analysis method. BB1639, annotated as a hypothetical protein, was identified as a novel type III secreted protein and was designated BspR (Bordetella secreted protein regulator. The virulence of a BspR mutant (ΔbspR in B. bronchiseptica was significantly attenuated in a mouse infection model. BspR was also highly conserved in B. pertussis and B. parapertussis, suggesting that BspR is an essential virulence factor in these three Bordetella species. Interestingly, the BspR-deficient strain showed hyper-secretion of T3SS-related proteins. Furthermore, T3SS-dependent host cell cytotoxicity and hemolytic activity were also enhanced in the absence of BspR. By contrast, the expression of filamentous hemagglutinin, pertactin, and adenylate cyclase toxin was completely abolished in the BspR-deficient strain. Finally, we demonstrated that BspR is involved in the iron-responsive regulation of T3SS. Thus, Bordetella virulence factors are coordinately but inversely controlled by BspR, which functions as a regulator in response to iron starvation.

  4. Complex Function for SicA, a Salmonella enterica Serovar Typhimurium Type III Secretion-Associated Chaperone

    OpenAIRE

    Tucker, Stephanie C.; Jorge E Galán

    2000-01-01

    Salmonella enterica encodes a type III secretion system within a pathogenicity island located at centisome 63 that is essential for virulence. All type III secretion systems require the function of a family of low-molecular-weight proteins that aid the secretion process by acting as partitioning factors and/or secretion pilots. One such protein is SicA, which is encoded immediately upstream of the type III secreted proteins SipB and SipC. We found that the absence of SicA results in the degra...

  5. Complex Function for SicA, a Salmonella enterica Serovar Typhimurium Type III Secretion-Associated Chaperone

    OpenAIRE

    Tucker, Stephanie C.; Galán, Jorge E.

    2000-01-01

    Salmonella enterica encodes a type III secretion system within a pathogenicity island located at centisome 63 that is essential for virulence. All type III secretion systems require the function of a family of low-molecular-weight proteins that aid the secretion process by acting as partitioning factors and/or secretion pilots. One such protein is SicA, which is encoded immediately upstream of the type III secreted proteins SipB and SipC. We found that the absence of SicA results in the degra...

  6. Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III

    NARCIS (Netherlands)

    Welling, Lindsey; Marchal, Jan Pieter; van Hasselt, Peter; van der Ploeg, Ans T; Wijburg, Frits A; Boelens, Jaap Jan

    2015-01-01

    Mucopolysaccharidosis type III (MPS III), or Sanfilippo disease, is a neurodegenerative lysosomal storage disease (LSD) caused by defective lysosomal degradation of heparan sulfate (HS). No effective disease-modifying therapy is yet available. In contrast to some other neuronopathic LSDs, bone marro

  7. Trabecular Metal Augments for the Management of Paprosky Type III Defects Without Pelvic Discontinuity.

    Science.gov (United States)

    Grappiolo, Guido; Loppini, Mattia; Longo, Umile Giuseppe; Traverso, Francesco; Mazziotta, Giuseppe; Denaro, Vincenzo

    2015-06-01

    Fifty-five hips undergoing acetabular reconstruction with trabecular metal (TM)-coated cup and TM augments were reviewed at an average follow up of 53.7 months (36-91). Bony defects were Paprosky type IIIA in 42 and type IIIB without pelvic discontinuity in 13 hips. The average HHS increased from 40 (27-52) preoperatively to 90.5 (61-100) postoperatively (P<0.0001). Four (7.3%) of 55 hips underwent acetabular components revision: three cases of loosening (5.4%), and one of recurrent instability (1.8%) were reported. Survival rate at 2 and 5 years was 96.4% and 92.8%. In conclusion, the use of TM-coated cups and augments could be considered an effective management of Paprosky type III defects without pelvic discontinuity providing good clinical and radiographic outcomes in the mid term.

  8. Beat-type Langmuir wave emissions associated with a type III solar radio burst: Evidence of parametric decay

    Science.gov (United States)

    Hospodarsky, G. B.; Gurnett, D. A.

    1995-01-01

    Recent measurements from the plasma wave instrument on the Galileo spacecraft have shown that Langmuir waves observed in conjunction with a type III solar radio burst contain many beat-type waveforms, with beat frequencies ranging from about 150 to 650 Hz. Strong evidence exists that the beat pattern is produced by two closely spaced narrowband components. The most likely candidates for these two waves are a beam-generated Langmuir wave and an oppositely propagating Langmuir wave produced by parametric decay. In the parametric decay process, nonlinear interactions cause the beam-driven Langmuir wave to decay into a Langmuir wave and a low-frequency ion sound wave. Comparisons of the observed beat frequency are in good agreement with theoretical predictions for a three-wave parametric decay process. Weak low-frequency emissions are also sometimes observed at the predicted frequency of the ion sound wave.

  9. Type-II/III DCT/DST algorithms with reduced number of arithmetic operations

    CERN Document Server

    Shao, Xuancheng

    2007-01-01

    We present algorithms for the discrete cosine transform (DCT) and discrete sine transform (DST), of types II and III, that achieve a lower count of real multiplications and additions than previously published algorithms, without sacrificing numerical accuracy. Asymptotically, the operation count is reduced from ~ 2N log_2 N to ~ (17/9) N log_2 N for a power-of-two transform size N. Furthermore, we show that a further N multiplications may be saved by a certain rescaling of the inputs or outputs, generalizing a well-known technique for N=8 by Arai et al. These results are derived by considering the DCT to be a special case of a DFT of length 4N, with certain symmetries, and then pruning redundant operations from a recent improved fast Fourier transform algorithm (based on a recursive rescaling of the conjugate-pair split radix algorithm). The improved algorithms for DCT-III, DST-II, and DST-III follow immediately from the improved count for the DCT-II.

  10. Type III polyketide synthase is involved in the biosynthesis of protocatechuic acid in Aspergillus niger.

    Science.gov (United States)

    Lv, Yangyong; Xiao, Jing; Pan, Li

    2014-11-01

    Genomic studies have shown that not only plants but also filamentous fungi contain type III polyketide synthases. To study the function of type III polyketide synthase (AnPKSIII) in Aspergillus niger, a deletion strain (delAnPKSIII) and an overexpression strain (oeAnPKSIII) were constructed in A. niger MA169.4, a derivative of the wild-type (WT) A. niger ATCC 9029 that produces large quantities of gluconic acid. Alterations in the metabolites were analyzed by HPLC when the extract of the overexpression strain was compared with extracts of the WT and deletion strains. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid, 3.2 mg/l) was isolated and identified as the main product of AnPKSIII when inductively expressed in A. niger MA169.4. The molecular weight of PCA was 154.1 (m/z 153.1 [M-H](-)), was detected by ESI-MS in the negative ionization mode, and (1)H and (13)C NMR data confirmed its structure.

  11. [Triple-Endobutton plates for the treatment of rockwood type III to V acromioclavicular joint dislocation].

    Science.gov (United States)

    Yin, Ji-Heng

    2014-01-01

    To evaluate the clinical results of Triple-Endobutton plates for the treatment of Rockwood type III to V acromioclavicular joint dislocation. From March 2008 to June 2010,28 patients with Rockwood type II to V acromioclavicular joint dislocations were treated with Triple-Endobutton plates. There were 18 males and 10 females,ranging in age from 20 to 60 years old (averaged 38 years old). Twenty patients had dislocations in the left and 8 patients had dislocations in the right. All the patients had close injury. The Constant criterion was used to evaluate shoulder joint function. All the patients were followed up,and the duration ranged from 18 to 24 months,with an average of 20 months. All the patients got good shoulder joint function,and no re-dislocation and pain occurred. The X-ray showed all acromioclavicular joints got good reduction. According to Constant criterion,preoperative score was 25.4 +/- 2.0, postoperative scores were 65.9 +/- 3.0, 87.2 +/- 3.2 and 95.7+/- 1.6 at 1 month,3 months and 6 months separately. Treatment of Rockwood type III to V acromioclavicular joint dislocation with Triple-Endobutton plates has satisfactory clinical outcome, simple operation, few complications, without secondary operation and early functional exercise postoperatively.

  12. Bounds on charged higgs boson in the 2HDM type III from Tevatron

    CERN Document Server

    Martínez, R; Rozo, M

    2003-01-01

    We consider the Two Higgs Doublet Model (2HDM) of type III which leads to Flavour Changing Neutral Currents (FCNC) at tree level. In the framework of this model we can use an appropriate form of the Yukawa Lagrangian that makes the type II model limit of the general type III couplings apparent. This way is useful in order to compare with the experimental data which is model dependent. The analytical expressions of the partial width $\\Gamma (t \\to H^+ b) $ are derived and we compare with the data available at this energy range. We examine the limits on the new parameter $\\lambda_{tt}$ from the validness criterium of perturbation theory and we get $\\lambda_{tt} \\geq \\sqrt{2} (1-\\tan \\beta)/\\sqrt{1+\\tan^2 \\beta}$. Furthermore, we analyze the perturbation theory limit together with experimental bounds on $B(t \\to H^+ b)$ and we get a bound on the charged Higgs mass, $m_{H^+}\\geq 123$ GeV.

  13. Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells

    DEFF Research Database (Denmark)

    Jensen, L T; Blaehr, H; Andersen, C B;

    1992-01-01

    Degradation of the intact form of the aminoterminal propeptide of type III procollagen (PIIINP) has been established in the liver, whereas the col 1 domain of PIIINP is extracted by the kidneys. We used native human PIIINP and col 1 domain of PIIINP to investigate the degradation of PIIINP...... in cultures of human proximal tubular cells. Normal renal tissue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was characterized by incubation of [125I]-PIIINP followed by gel filtration. We found that in physiological...

  14. The rare decay $t \\to c \\gamma$ in the General 2HDM type III

    CERN Document Server

    Díaz, R A; Rodríguez, José Alberto; Diaz, Rodolfo A.

    2001-01-01

    We consider the branching ratio for the process $t \\to c \\gamma$ in the context of the General Two Higgs Doublet Model type III. We find that taking into account reasonable values for the parameter $\\tan \\beta$ is possible to get values of this branching ratio up to orders of magnitude lying in the range of sensitivity of near future top quark experiments. For values of $B(t \\to c \\gamma) \\sim 1-9 \\times 10^{-5}$, values between 8-15 for $\\tan \\beta$ are allowed.

  15. Endodontic treatment of a periradicular lesion on an invaginated type III mandibular lateral incisor

    Directory of Open Access Journals (Sweden)

    Carvalho-Sousa B

    2009-01-01

    Full Text Available Dens invaginatus (DI, commonly known as dens in dente, is a developmental malformation of teeth that most commonly affects permanent maxillary incisor teeth. DI can present in a variety of forms, knowledge of which can usefully help in endodontic diagnosis and treatment. This article reports on an unusual case of DI type III with a periradicular lesion in a mandibular lateral incisor. Non-surgical endodontic treatment was performed and resolution of the periradicular lesion was observed at 1 year follow-up. Clinical considerations and treatment are discussed and reported.

  16. Developmental defects in a Caenorhabditis elegans model for type III galactosemia.

    Science.gov (United States)

    Brokate-Llanos, Ana M; Monje, José M; Murdoch, Piedad Del Socorro; Muñoz, Manuel J

    2014-12-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosylation process. We also observed that gale-1 mutants are hypersensitive to galactose as well as to infections. Interestingly, we found interactions between gale-1 and the unfolded protein response.

  17. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  18. Tyrosinemia type III: diagnosis and ten-year follow-up.

    Science.gov (United States)

    Cerone, R; Holme, E; Schiaffino, M C; Caruso, U; Maritano, L; Romano, C

    1997-09-01

    Tyrosinemia type III, caused by deficiency of 4-hydroxyphenylpyruvate dioxygenase, is a rare disorder of tyrosine catabolism. Primary 4-hydroxyphenylpyruvate dioxygenase deficiency has been described in only three patients. The biochemical phenotype shows hypertyrosinemia and elevated urinary excretion of 4-hydroxyphenyl derivatives. We report the clinical and biochemical findings and the results of long-term follow-up in a new patient with this disorder presenting with severe mental retardation and neurological abnormalities. The clinical phenotype is compared with those reported in the three previously described patients.

  19. [Pavlik harness for the treatment of congenital hip dysplasia types D III and IV].

    Science.gov (United States)

    Zajonz, D; Strobel, S; Wojan, M; von der Höh, N; Brandmaier, P; Josten, C; Schumann, E; Heyde, C-E

    2016-01-01

    Up to 4% of all neonates in Central Europe are born with congenital hip dysplasia (CHD), the most common congenital disease of the musculoskeletal system. However, in this retrospective analysis the outcomes of infants with CHD (type D, III or IV according to Graf) have been considered, with Pavlik therapy starting within the first 12 weeks of life. Connections between the start of therapy or the first finding according to Graf`s classification and the ultrasound result achieved, as well as the X-rays taken after 1 and 2 years, were evaluated. No repositioning under Pavlik treatment or side effects and their relevance have been evaluated, especially with regard to avascular necrosis (AVN) of the femoral head. All infants treated using Pavlik treatment for CHD between 2010 and 2012 in our clinic were determined. A total of 62 patients with 79 pathological hips were included. The infants were classified into three groups to evaluate the influence of the start of therapy on the result: group I with the first investigation and start of treatment within the first 10 days of life, group II between the 11th day and the end of week 3, group III within preventive general examinations (U3) after the 4th week. Clinical examinations and the usual ultrasound scans were performed at an average of 1, 3, and 6 months. Furthermore, after 1 and 2 years clinical and radiological investigations were carried out, as well as further examinations depending on the findings. A failure of repositioning of the Pavlik treatment occurred in group I in 1 case (2.2%), in group II in 1 case (7.1%), and in group III in 2 cases (10%). This occurs in hips type D and type III in 1 case each (3.3%) and type IV in 2 cases (10.5%). Maturation disorders of the hips were found in 1 case (2.2%) in group I, 1 case (7.1%) in group II, and 3 cases (15%) in group III. Avascular necrosis of the femoral head was proven in 2 cases (4.4%) in group I, 0% in group II, and in 1 case (5%) in group III. All patients

  20. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  1. Structure-function relationships within Keppler-type antitumor ruthenium(III) complexes: the case of 2-aminothiazolium[trans-tetrachlorobis(2-aminothiazole)ruthenate(III)].

    Science.gov (United States)

    Mura, Pasquale; Piccioli, Francesca; Gabbiani, Chiara; Camalli, Mercedes; Messori, Luigi

    2005-07-11

    Keppler-type ruthenium(III) complexes exhibit promising antitumor properties. We report here a study of 2-aminothiazolium[trans-tetrachlorobis(2-aminothiazole)ruthenate(III)], both in the solid state and in solution. The crystal structure has been solved and found to exhibit classical features. Important solvatochromic effects were revealed. Notably, we observed that introduction of an amino group in position 2 greatly accelerates chloride hydrolysis compared to the thiazole analogue; this latter finding may be of interest for a fine-tuning of the reactivity of these novel metallodrugs.

  2. Collagen Type III and VI Turnover in Response to Long-Term Immobilization.

    Directory of Open Access Journals (Sweden)

    Shu Sun

    Full Text Available Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization.In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage.Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization.The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.

  3. Influence of geochemical properties and land-use types on the microbial reduction of Fe(III) in subtropical soils.

    Science.gov (United States)

    Liu, Chengshuai; Wang, Yongkui; Li, Fangbai; Chen, Manjia; Zhai, Guangshu; Tao, Liang; Liu, Chuanping

    2014-08-01

    Microbial Fe(III) reduction significantly impacts the geochemical processes and the composition of most subsurface soils. However, up to now, the factors influencing the efficiency of Fe(III) reduction in soils have not been fully described. In this study, soil Fe(III) reduction processes related to geochemical properties and land-use types were systematically investigated using iron-rich soils. The results showed that microbial Fe(III) reduction processes were efficient and their rates varied significantly in different types of soils. Fe(III) reduction rates were 1.1-5.6 times as much in soils with glucose added as in those without glucose. Furthermore, Fe(III) reduction rates were similar in soils from the same parent materials, while they were highest in soils developed from sediments, with a mean rate of 1.87 mM per day when supplemented with glucose. In addition, the Fe(III) reduction rates, reaching 0.99 and 0.59 mM per day on average with and without glucose added, respectively, were higher in the paddy soils affected heavily by human activities than those in the forest soils (average rates of 0.38 and 0.15 mM per day when with and without glucose, respectively). All the soil weathering indices correlated linearly with Fe(III) reduction rates, even though the reduction of iron in soils with higher weathering degrees was partly inhibited by a higher soil protonation trend and fewer available iron reduction sites in the soils, which gives lower reduction rates. These results clearly illustrate that soil Fe(III) reduction rates are greatly dependent on soil geochemical properties and land-use types and help define which soil types exhibit similar degrees of Fe(III) reduction under field conditions.

  4. Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

    Directory of Open Access Journals (Sweden)

    Alice D. Chang

    2006-01-01

    Full Text Available We studied a 14 year-old boy with partial DiGeorge syndrome (DGS, status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT. Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF, and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF. This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  5. High frequency ion sound waves associated with Langmuir waves in type III radio burst source regions

    Directory of Open Access Journals (Sweden)

    G. Thejappa

    2004-01-01

    Full Text Available Short wavelength ion sound waves (2-4kHz are detected in association with the Langmuir waves (~15-30kHz in the source regions of several local type III radio bursts. They are most probably not due to any resonant wave-wave interactions such as the electrostatic decay instability because their wavelengths are much shorter than those of Langmuir waves. The Langmuir waves occur as coherent field structures with peak intensities exceeding the Langmuir collapse thresholds. Their scale sizes are of the order of the wavelength of an ion sound wave. These Langmuir wave field characteristics indicate that the observed short wavelength ion sound waves are most probably generated during the thermalization of the burnt-out cavitons left behind by the Langmuir collapse. Moreover, the peak intensities of the observed short wavelength ion sound waves are comparable to the expected intensities of those ion sound waves radiated by the burnt-out cavitons. However, the speeds of the electron beams derived from the frequency drift of type III radio bursts are too slow to satisfy the needed adiabatic ion approximation. Therefore, some non-linear process such as the induced scattering on thermal ions most probably pumps the beam excited Langmuir waves towards the lower wavenumbers, where the adiabatic ion approximation is justified.

  6. Type III mixed cryoglobulinemia and antiphospholipid syndrome in a patient with partial DiGeorge syndrome.

    Science.gov (United States)

    Chang, Alice D; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K; Lassman, Charles; Stiehm, E Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated beta(2)-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  7. Adenocarcinoma arising in a heterotopic pancreas (Heinrich type III: a case report

    Directory of Open Access Journals (Sweden)

    Egashira Yutaro

    2010-02-01

    Full Text Available Abstract Introduction Heterotopic pancreatic cancer in the duodenum is a very rare disease. Only twelve cases have been reported worldwide to date. We report a rare case of malignant transformation of heterotopic pancreas (Heinrich type III in the duodenum with long-term survival of the patient, and review the 12 cases in the literature. Case presentation A 75-year-old Japanese man was admitted to our hospital complaining of nausea and vomiting. Endoscopy and upper gastrointestinal contrast study showed marked duodenal stenosis. A pylorus-preserving pancreaticoduodenectomy was performed. Histopathological examination of the surgically resected specimen showed malignant transformation of heterotopic pancreas (Heinrich type III in the duodenum. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 30. He is well and shows no signs of recurrence at the time of writing, six years after the surgery. Conclusion Adenocarcinoma arising within the heterotopic pancreas appears to be rare. It is difficult to obtain a correct diagnosis preoperatively. The management of heterotopic pancreas depends on the presence or absence of symptoms. If the patient is asymptomatic or benign, conservative treatment with regular follow-up is recommended. When the patient is symptomatic or there is a suspicion of malignancy, surgical management with intra-operative frozen section diagnosis is indicated.

  8. LOFAR tied-array imaging of Type III solar radio bursts

    CERN Document Server

    Morosan, D E; Zucca, P; Fallows, R; Carley, E P; Mann, G; Bisi, M M; Kerdraon, A; Konovalenko, A A; MacKinnon, A L; Rucker, H O; Thidé, B; Magdalenić, J; Vocks, C; Reid, H; Anderson, J; Asgekar, A; Avruch, I M; Bentum, M J; Bernardi, G; Best, P; Bonafede, A; Bregman, J; Breitling, F; Broderick, J; Brüggen, M; Butcher, H R; Ciardi, B; Conway, J E; de Gasperin, F; de Geus, E; Deller, A; Duscha, S; Eislöffel, J; Engels, D; Falcke, H; Ferrari, C; Frieswijk, W; Garrett, M A; Grießmeier, J; Gunst, A W; Hassall, T E; Hessels, J W T; Hoeft, M; Hörandel, J; Horneffer, A; Iacobelli, M; Juette, E; Karastergiou, A; Kondratiev, V I; Kramer, M; Kuniyoshi, M; Kuper, G; Maat, P; Markoff, S; McKean, J P; Mulcahy, D D; Munk, H; Nelles, A; Norden, M J; Orru, E; Paas, H; Pandey-Pommier, M; Pandey, V N; Pietka, G; Pizzo, R; Polatidis, A G; Reich, W; Röttgering, H; Scaife, A M M; Schwarz, D; Serylak, M; Smirnov, O; Stappers, B W; Stewart, A; Tagger, M; Tang, Y; Tasse, C; Thoudam, S; Toribio, C; Vermeulen, R; van Weeren, R J; Wucknitz, O; Yatawatta, S; Zarka, P

    2014-01-01

    The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), the Sun has not been imaged extensively because of the instrumental limitations of previous radio telescopes. Here, the combined high spatial, spectral and temporal resolution of the Low Frequency Array (LOFAR) was used to study solar Type III radio bursts at 30-90 MHz and their association with CMEs. The Sun was imaged with 126 simultaneous tied-array beams within 5 solar radii of the solar centre. This method offers benefits over standard interferometric imaging since each beam produces high temporal (83 ms) and spectral resolution (12.5 kHz) dynamic spectra at an array of spatial locations centred on the Sun. LOFAR's standard interferometric output is currently limited to one image per second. Over a period of 30 minutes, multiple Type III radio bursts were observed, a number of which were found to be located at high...

  9. Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain.

    Directory of Open Access Journals (Sweden)

    Laura De Laporte

    Full Text Available Tenascin C (TNC is an extracellular matrix protein that is upregulated during development as well as tissue remodeling. TNC is comprised of multiple independent folding domains, including 15 fibronectin type III-like (TNCIII domains. The fifth TNCIII domain (TNCIII5 has previously been shown to bind heparin. Our group has shown that the heparin-binding fibronectin type III domains of fibronectin (FNIII, specifically FNIII12-14, possess affinity towards a large number of growth factors. Here, we show that TNCIII5 binds growth factors promiscuously and with high affinity. We produced recombinant fragments of TNC representing the first five TNCIII repeats (TNCIII1-5, as well as subdomains, including TNCIII5, to study interactions with various growth factors. Multiple growth factors of the platelet-derived growth factor (PDGF family, the fibroblast growth factor (FGF family, the transforming growth factor beta (TGF-β superfamily, the insulin-like growth factor binding proteins (IGF-BPs, and neurotrophins were found to bind with high affinity to this region of TNC, specifically to TNCIII5. Surface plasmon resonance was performed to analyze the kinetics of binding of TNCIII1-5 with TGF-β1, PDGF-BB, NT-3, and FGF-2. The promiscuous yet high affinity of TNC for a wide array of growth factors, mediated mainly by TNCIII5, may play a role in multiple physiological and pathological processes involving TNC.

  10. Pore-forming Activity of the Escherichia coli Type III Secretion System Protein EspD.

    Science.gov (United States)

    Chatterjee, Abhishek; Caballero-Franco, Celia; Bakker, Dannika; Totten, Stephanie; Jardim, Armando

    2015-10-16

    Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280-320-kDa oligomeric structure consisting of ∼6-7 subunits.

  11. A quantitative infection assay for human type I, II, and III interferon antiviral activities

    Science.gov (United States)

    2013-01-01

    Background Upon virus infection, cells secrete a diverse group of antiviral molecules that signal proximal cells to enter into an antiviral state, slowing or preventing viral spread. These paracrine signaling molecules can work synergistically, so measurement of any one antiviral molecule does not reflect the total antiviral activity of the system. Results We have developed an antiviral assay based on replication inhibition of an engineered fluorescent vesicular stomatitis virus reporter strain on A549 human lung epithelial cells. Our assay provides a quantitative functional readout of human type I, II, and III interferon activities, and it provides better sensitivity, intra-, and inter-assay reproducibility than the traditional crystal violet based assay. Further, it eliminates cell fixation, rinsing, and staining steps, and is inexpensive to implement. Conclusions A dsRed2-strain of vesicular stomatitis virus that is sensitive to type I, II, and III interferons was used to develop a convenient and sensitive assay for interferon antiviral activity. We demonstrate use of the assay to quantify the kinetics of paracrine antiviral signaling from human prostate cancer (PC3) cells in response to viral infection. The assay is applicable to high-throughput screening for anti-viral compounds as well as basic studies of cellular antiviral signaling. PMID:23829314

  12. Extended SUSY SU(5) predicting type-III seesaw testable at LHC

    CERN Document Server

    Awasthi, Ram Lal

    2013-01-01

    We propose an extension of the SUSY SU(5) which predicts LHC testable type-III seesaw. The supersymmetric SU(5) GUT model is extended by adding a 24-plet matter superfield along with a pair of $10_H$-plet and $\\bar{10}_H$-plet Higgs superfields. The 24-plet carries a triplet and a singlet fermion multiplet of SU(2)$_L$, which leads to type I+III seesaw. The additional $10_H$ (and $\\bar{10}_H$) multiplets help in achieving gauge coupling unification while keeping the triplet fermion mass in the TeV range, making them accessible at LHC. We study the phenomenology of this model in detail. Large lepton flavor violation predicted in this model puts severe constraints on the Yukawa couplings of the triplet fermion. We show that this smothers the possibility of observing the contribution of the heavy fermions in neutrinoless double beta decay experiments. The presence of the additional $10_H$ and $\\bar{10}_H$ in this model not only gives gauge coupling unification, it also leads to very large lepton flavor violation...

  13. Plant flavonoids target Pseudomonas syringae pv. tomato DC3000 flagella and type III secretion system.

    Science.gov (United States)

    Vargas, Paola; Farias, Gabriela A; Nogales, Joaquina; Prada, Harold; Carvajal, Vivian; Barón, Matilde; Rivilla, Rafael; Martín, Marta; Olmedilla, Adela; Gallegos, María-Trinidad

    2013-12-01

    Flavonoids are among the most abundant plant secondary metabolites involved in plant protection against pathogens, but micro-organisms have developed resistance mechanisms to those compounds. We previously demonstrated that the MexAB-OprM efflux pump mediates resistance of Pseudomonas syringae pv. tomato (Pto) DC3000 to flavonoids, facilitating its survival and the colonization of the host. Here, we have shown that tomato plants respond to Pto infection producing flavonoids and other phenolic compounds. The effects of flavonoids on key traits of this model plant-pathogen bacterium have also been investigated observing that they reduce Pto swimming and swarming because of the loss of flagella, and also inhibited the expression and assembly of a functional type III secretion system. Those effects were more severe in a mutant lacking the MexAB-OprM pump. Our results suggest that flavonoids inhibit the function of the GacS/GacA two-component system, causing a depletion of rsmY RNA, therefore affecting the synthesis of two important virulence factors in Pto DC3000, flagella and the type III secretion system. These data provide new insights into the flavonoid role in the molecular dialog between host and pathogen.

  14. Immunomodulation by the Pseudomonas syringae HopZ type III effector family in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jennifer D Lewis

    Full Text Available Pseudomonas syringae employs a type III secretion system to inject 20-30 different type III effector (T3SE proteins into plant host cells. A major role of T3SEs is to suppress plant immune responses and promote bacterial infection. The YopJ/HopZ acetyltransferases are a superfamily of T3SEs found in both plant and animal pathogenic bacteria. In P. syringae, this superfamily includes the evolutionarily diverse HopZ1, HopZ2 and HopZ3 alleles. To investigate the roles of the HopZ family in immunomodulation, we generated dexamethasone-inducible T3SE transgenic lines of Arabidopsis for HopZ family members and characterized them for immune suppression phenotypes. We show that all of the HopZ family members can actively suppress various facets of Arabidopsis immunity in a catalytic residue-dependent manner. HopZ family members can differentially suppress the activation of mitogen-activated protein (MAP kinase cascades or the production of reactive oxygen species, whereas all members can promote the growth of non-virulent P. syringae. Localization studies show that four of the HopZ family members containing predicted myristoylation sites are localized to the vicinity of the plasma membrane while HopZ3 which lacks the myristoylation site is at least partially nuclear localized, suggesting diversification of immunosuppressive mechanisms. Overall, we demonstrate that despite significant evolutionary diversification, all HopZ family members can suppress immunity in Arabidopsis.

  15. LOFAR tied-array imaging of Type III solar radio bursts

    Science.gov (United States)

    Morosan, D. E.; Gallagher, P. T.; Zucca, P.; Fallows, R.; Carley, E. P.; Mann, G.; Bisi, M. M.; Kerdraon, A.; Konovalenko, A. A.; MacKinnon, A. L.; Rucker, H. O.; Thidé, B.; Magdalenić, J.; Vocks, C.; Reid, H.; Anderson, J.; Asgekar, A.; Avruch, I. M.; Bentum, M. J.; Bernardi, G.; Best, P.; Bonafede, A.; Bregman, J.; Breitling, F.; Broderick, J.; Brüggen, M.; Butcher, H. R.; Ciardi, B.; Conway, J. E.; de Gasperin, F.; de Geus, E.; Deller, A.; Duscha, S.; Eislöffel, J.; Engels, D.; Falcke, H.; Ferrari, C.; Frieswijk, W.; Garrett, M. A.; Grießmeier, J.; Gunst, A. W.; Hassall, T. E.; Hessels, J. W. T.; Hoeft, M.; Hörandel, J.; Horneffer, A.; Iacobelli, M.; Juette, E.; Karastergiou, A.; Kondratiev, V. I.; Kramer, M.; Kuniyoshi, M.; Kuper, G.; Maat, P.; Markoff, S.; McKean, J. P.; Mulcahy, D. D.; Munk, H.; Nelles, A.; Norden, M. J.; Orru, E.; Paas, H.; Pandey-Pommier, M.; Pandey, V. N.; Pietka, G.; Pizzo, R.; Polatidis, A. G.; Reich, W.; Röttgering, H.; Scaife, A. M. M.; Schwarz, D.; Serylak, M.; Smirnov, O.; Stappers, B. W.; Stewart, A.; Tagger, M.; Tang, Y.; Tasse, C.; Thoudam, S.; Toribio, C.; Vermeulen, R.; van Weeren, R. J.; Wucknitz, O.; Yatawatta, S.; Zarka, P.

    2014-08-01

    Context. The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (benefits over standard interferometric imaging since each beam produces high temporal (~83 ms) and spectral resolution (12.5 kHz) dynamic spectra at an array of spatial locations centred on the Sun. LOFAR's standard interferometric output is currently limited to one image per second. Results: Over a period of 30 min, multiple Type III radio bursts were observed, a number of which were found to be located at high altitudes (~4 R⊙ from the solar center at 30 MHz) and to have non-radial trajectories. These bursts occurred at altitudes in excess of values predicted by 1D radial electron density models. The non-radial high altitude Type III bursts were found to be associated with the expanding flank of a CME. Conclusions: The CME may have compressed neighbouring streamer plasma producing larger electron densities at high altitudes, while the non-radial burst trajectories can be explained by the deflection of radial magnetic fields as the CME expanded in the low corona. Movie associated to Fig. 2 is available in electronic form at http://www.aanda.org

  16. Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris

    Directory of Open Access Journals (Sweden)

    Guo-Feng Jiang

    2013-09-01

    Full Text Available It is well known that the type III secretion system (T3SS and type III (T3 effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2 which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2 is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME. Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.

  17. Delayed fixation of displaced type II and III pediatric femoral neck fractures

    Directory of Open Access Journals (Sweden)

    Azam Md

    2009-01-01

    Full Text Available Background: Time from injury to fixation of femoral neck fractures has been postulated as a vital determinant for rate of complications; however, no prospective study is available in the English literature. Delay, unfortunately, is inevitable in developing countries. The aim of the present study is to retrospectively review the outcome after delayed fixation of displaced type II and III femoral neck fractures in children. Materials and Methods: Using a standard assessment chart, we retrospectively reviewed medical records of all pediatric patients having femoral neck fractures presenting to our institution from June 1999 to May 2006. Inclusion criteria were children between 5 and 15 years of age sustaining displaced Delbet type II and III femoral neck fractures having a complete follow-up of at least 2 years. Patients with known metabolic disease, poliomyelitis or cerebral palsy, were excluded from the study. After application of inclusion and exclusion criteria, 22 patients having 22 fractures (13 type II and 9 type III were studied. Surgery could be performed after a mean delay of 11.22 days (ranging from 2 to 21 days. Closed reduction was achieved in 14 cases and 8 cases required open reduction through anterolateral approach. Result: Osteonecrosis was noted in eight patients (36.37% who included two of nine patients (22.22% operated in the first week, three of eight patients (37.51% operated in the second week, and three of five patients (60% operated in the third week of injury. Nonunion was seen in four (18.18% cases, and two of them were associated with failure of implants. One was treated by valgus osteotomy and the other by Meyer′s procedure. Fractures united in both children but the latter developed avascular necrosis. Functional results, as assessed using Ratliff′s criteria, were good in 14 (63.63%, fair in 2 (9%, and poor in 6 (27.27% patients. Conclusion: Delay in fixation, type of fracture, and ability to achieve and maintain

  18. Propionibacterium Acnes Phylogenetic Type III is Associated with Progressive Macular Hypomelanosis

    DEFF Research Database (Denmark)

    Petersen, Rolf L W; Scholz, Christian F P; Jensen, Anders

    2017-01-01

    Progressive macular hypomelanosis (PMH) is a skin disorder that is characterized by hypopigmented macules and usually seen in young adults. The skin microbiota, in particular the bacterium Propionibacterium acnes, is suggested to play a role. Here, we compared the P. acnes population of 24 PMH...... lesions from eight patients with corresponding nonlesional skin of the patients and matching control samples from eight healthy individuals using an unbiased, culture-independent next-generation sequencing approach. We also compared the P. acnes population before and after treatment with a combination...... of lymecycline and benzoylperoxide. We found an association of one subtype of P. acnes, type III, with PMH. This type was predominant in all PMH lesions (73.9% of reads in average) but only detected as a minor proportion in matching control samples of healthy individuals (14.2% of reads in average). Strikingly...

  19. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli

    1997-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...... from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical...... techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma...

  20. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli

    1997-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...... from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical...... techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma...

  1. Leukocyte adhesion deficiency type III: clinical features and treatment with stem cell transplantation.

    Science.gov (United States)

    Stepensky, Polina Y; Wolach, Baruch; Gavrieli, Ronit; Rousso, Sharon; Ben Ami, Tal; Goldman, Vladimir; Rozovsky, Katya; Hanna, Suhair; Etzioni, Amos; Weintraub, Michael

    2015-05-01

    Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive disorder that presents with a severe leukocyte adhesion defect and a Glanzmann-type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only definitive treatment for LADIII--appears to have a high rate of complications. In this study, we describe a new group of patients with LADIII, highlighting further clinical and immunologic aspects of this disease, and reevaluating the effectiveness of HSCT for its treatment. The patients had clinical and laboratory findings consistent with LADIII. Molecular analysis confirmed the presence of a mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was successful in 2. The diagnosis of LADIII should be considered in all patients who present with recurrent infections and a bleeding diathesis, regardless of the leukocyte count. LADIII is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of the disease using appropriate conditioning.

  2. Type III Osteogenesis Imperfecta With Dentinogenesis Imperfecta - A Case Report And review of Literature

    Directory of Open Access Journals (Sweden)

    Prabal Pal

    2003-01-01

    Full Text Available Osteogenesis Imperfecta is a genetic disorder affecting approximately 20,000 U.S. population with multiple fracture of the bone. The, actual literature of the number of patients suffering from Osteogenesis Impcrfecta in Indian Population is still nor available. This is a case of a male patient who presented to the O.PD. of Subharati Dental College with history of pain ands swelling in the left lower posterior teeth region. On detail workout of the case it was found that the patient had Dentinogenesis Imperfecta Type I with Type III Osteogenesis Imperfecta. Very few cases with such presentation is reported in Indian Literature. The following report presents the clinical findings of Osteogcnesis Imperfecta and an associated review of Literature.

  3. Role of NSO compounds during primary cracking of a Type II kerogen and a Type III lignite

    Science.gov (United States)

    Behar, F.; Lorant, F.; Lewan, M.

    2008-01-01

    The aim of this work is to follow the generation of NSO compounds during the artificial maturation of an immature Type II kerogen and a Type III lignite in order to determine the different sources of the petroleum potential during primary cracking. Experiments were carried out in closed system pyrolysis in the temperature range from 225 to 350 ??C. Two types of NSOs were recovered: one is soluble in n-pentane and the second in dichloromethane. A kinetic scheme was optimised including both kerogen and NSO cracking. It was validated by complementary experiments carried out on isolated asphaltenes generated from the Type II kerogen and on the total n-pentane and DCM extracts generated from the Type III lignite. Results show that kerogen and lignite first decompose into DCM NSOs with minor generation of hydrocarbons. Then, the main source of petroleum potential originates from secondary cracking of both DCM and n-pentane NSOs through successive decomposition reactions. These results confirm the model proposed by Tissot [Tissot, B., 1969. Premie??res donne??es sur les me??canismes et la cine??tique de la formation du pe??trole dans les bassins se??dimentaires. Simulation d'un sche??ma re??actionnel sur ordinateur. Oil and Gas Science and Technology 24, 470-501] in which the main source of hydrocarbons is not the insoluble organic matter, but the NSO fraction. As secondary cracking of the NSOs largely overlaps that of the kerogen, it was demonstrated that bulk kinetics in open system is a result of both kerogen and NSO cracking. Thus, another kinetic scheme for primary cracking in open system was built as a combination of kerogen and NSO cracking. This new kinetic scheme accounts for both the rate and amounts of hydrocarbons generated in a closed pyrolysis system. Thus, the concept of successive steps for hydrocarbon generation is valid for the two types of pyrolysis system and, for the first time, a common kinetic scheme is available for extrapolating results to natural

  4. Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.

    Directory of Open Access Journals (Sweden)

    José Luis Graña

    Full Text Available This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%, moderate (27.8% and high (7.1%. This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types.

  5. Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia.

    Directory of Open Access Journals (Sweden)

    Dimitra Georgiadou

    Full Text Available BACKGROUND: Apolipoprotein E (apoE is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL FINDINGS: In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may

  6. Type- and Subcomplex-Specific Neutralizing Antibodies against Domain III of Dengue Virus Type 2 Envelope Protein Recognize Adjacent Epitopes▿

    Science.gov (United States)

    Sukupolvi-Petty, Soila; Austin, S. Kyle; Purtha, Whitney E.; Oliphant, Theodore; Nybakken, Grant E.; Schlesinger, Jacob J.; Roehrig, John T.; Gromowski, Gregory D.; Barrett, Alan D.; Fremont, Daved H.; Diamond, Michael S.

    2007-01-01

    Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials. PMID:17881453

  7. Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes.

    Science.gov (United States)

    Sukupolvi-Petty, Soila; Austin, S Kyle; Purtha, Whitney E; Oliphant, Theodore; Nybakken, Grant E; Schlesinger, Jacob J; Roehrig, John T; Gromowski, Gregory D; Barrett, Alan D; Fremont, Daved H; Diamond, Michael S

    2007-12-01

    Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

  8. Spectroscopic Identification of Type 2 Quasars at Z < 1 in SDSS-III/BOSS

    CERN Document Server

    Yuan, Sihan; Zakamska, Nadia L

    2016-01-01

    The physics and demographics of type 2 quasars remain poorly understood, and new samples of such objects selected in a variety of ways can give insight into their physical properties, evolution, and relationship to their host galaxies. We present a sample of 2758 type 2 quasars at z $\\leq$ 1 from the SDSS-III/BOSS spectroscopic database, selected on the basis of their emission-line properties. We probe the luminous end of the population by requiring the rest-frame equivalent width of [OIII] to be > 100 {\\AA}. We distinguish our objects from star-forming galaxies and type 1 quasars using line widths, standard emission line ratio diagnostic diagrams at z 0.52. The majority of our objects have [OIII] luminosities in the range 10^8.5-10^10 L$_{\\odot}$ and redshifts between 0.4 and 0.65. Our sample includes over 400 type 2 quasars with incorrectly measured redshifts in the BOSS database; such objects often show kinematic substructure or outflows in the [OIII] line. The majority of the sample has counterparts in t...

  9. Treatment of Rockwood type III acromioclavicular joint dislocation using autogenous semitendinosus tendon graft and endobutton technique

    Directory of Open Access Journals (Sweden)

    Ye G

    2016-01-01

    Full Text Available Gang Ye, Chao-An Peng, Hua-Bin Sun, Jing Xiao, Kang Zhu Department of Orthopedics, the People’s Hospital of Huangpi District, Wuhan City, People’s Republic of China Background: The aim of this study was to evaluate the therapeutic effect of autogenous semitendinosus graft and endobutton technique, and compare with hook plate in treatment of Rockwood type III acromioclavicular (AC joint dislocation.Methods: From April 2012 to April 2013, we treated 46 patients with Rockwood type III AC joint dislocation. Patients were randomly divided into two groups: Group A was treated using a hook plate and Group B with autogenous semitendinosus graft and endobutton technique. All participants were followed up for 12 months. Radiographic examinations were performed every 2 months postoperatively, and clinical evaluation was performed using the Constant–Murley score at the last follow-up.Results: Results indicated that patients in Group B showed higher mean scores (90.3±5.4 than Group A (80.4±11.5 in terms of Constant–Murley score (P=0.001. Group B patients scored higher in terms of pain (P=0.002, activities (P=0.02, range of motion (P<0.001, and strength (P=0.004. In Group A, moderate pain was reported by 2 (8.7% and mild pain by 8 (34.8% patients. Mild pain was reported by 1 (4.3% patient in Group B. All patients in Group B maintained complete reduction, while 2 (8.7% patients in Group A experienced partial reduction loss. Two patients (8.7% encountered acromial osteolysis on latest radiographs, with moderate shoulder pain and limited range of motion.Conclusion: Autogenous semitendinosus graft and endobutton technique showed better results compared with the hook plate method and exhibited advantages of fewer complications such as permanent pain and acromial osteolysis. Keywords: Rockwood type III acromioclavicular joint dislocation, autogenous semitendinosus graft, endobutton, hook plate

  10. Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

    Directory of Open Access Journals (Sweden)

    Érika Satomi

    2008-01-01

    Full Text Available INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

  11. Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Travar, Maja; Petkovic, Miroslav; Verhaz, Antonija

    2016-02-01

    Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-α and IFN-β synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-γ has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, γδ T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-γ in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-γ. The balance between IFN-γ and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-γ responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up-regulation of IFN-λ genes in vitro. IFN-λs also have a role in modulation of Th1/Th2 response. IFN-λs are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen.

  12. Relationship of type III radio bursts with quasi-periodic pulsations in a solar flare

    CERN Document Server

    Kupriyanova, E G; Reid, H A S; Myagkova, I N

    2016-01-01

    We studied a solar flare with pronounced quasi-periodic pulsations detected in the microwave, X-ray, and radio bands. We used the methods of correlation, Fourier, and wavelet analyses to examine the temporal fine structures and relationships between the time profiles in each wave band. We found that the time profiles of the microwaves, hard X-rays and type III radio bursts vary quasi-periodically with the common period of 40-50 s. The average amplitude of the variations is high, above 30% of the background flux level and reaching 80% after the flare maximum. We did not find the periodicity in either the thermal X-ray flux component or source size dynamics. Our findings indicate that the detected periodicity is likely to be associated with periodic dynamics in the injection of non-thermal electrons, that can be produced by periodic modulation of magnetic reconnection.

  13. A common assembly module in injectisome and flagellar type III secretion sorting platforms.

    Science.gov (United States)

    Notti, Ryan Q; Bhattacharya, Shibani; Lilic, Mirjana; Stebbins, C Erec

    2015-05-21

    Translocating proteins across the double membrane of Gram-negative bacteria, type III secretion systems (T3SS) occur in two evolutionarily related forms: injectisomes, delivering virulence factors into host cells, and the flagellar system, secreting the polymeric filament used for motility. While both systems share related elements of a cytoplasmic sorting platform that facilitates the hierarchical secretion of protein substrates, its assembly and regulation remain unclear. Here we describe a module mediating the assembly of the sorting platform in both secretion systems, and elucidate the structural basis for segregation of homologous components among these divergent T3SS subtypes sharing a common cytoplasmic milieu. These results provide a foundation for the subtype-specific assembly of T3SS sorting platforms and will support further mechanistic analysis and anti-virulence drug design.

  14. Cif type III effector protein: a smart hijacker of the host cell cycle.

    Science.gov (United States)

    Samba-Louaka, Ascel; Taieb, Frédéric; Nougayrède, Jean-Philippe; Oswald, Eric

    2009-09-01

    During coevolution with their hosts, bacteria have developed functions that allow them to interfere with the mechanisms controlling the proliferation of eukaryotic cells. Cycle inhibiting factor (Cif) is one of these cyclomodulins, the family of bacterial effectors that interfere with the host cell cycle. Acquired early during evolution by bacteria isolated from vertebrates and invertebrates, Cif is an effector protein of type III secretion machineries. Cif blocks the host cell cycle in G1 and G2 by inducing the accumulation of the cyclin-dependent kinase inhibitors p21(waf1/cip1) and p27(kip1). The x-ray crystal structure of Cif reveals it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases. This review summarizes and discusses what we know about Cif, from the bacterial gene to the host target.

  15. Bacterial flagella and Type III secretion: case studies in the evolution of complexity.

    Science.gov (United States)

    Pallen, M J; Gophna, U

    2007-01-01

    Bacterial flagella at first sight appear uniquely sophisticated in structure, so much so that they have even been considered 'irreducibly complex' by the intelligent design movement. However, a more detailed analysis reveals that these remarkable pieces of molecular machinery are the product of processes that are fully compatible with Darwinian evolution. In this chapter we present evidence for such processes, based on a review of experimental studies, molecular phylogeny and microbial genomics. Several processes have played important roles in flagellar evolution: self-assembly of simple repeating subunits, gene duplication with subsequent divergence, recruitment of elements from other systems ('molecular bricolage'), and recombination. We also discuss additional tentative new assignments of homology (FliG with MgtE, FliO with YscJ). In conclusion, rather than providing evidence of intelligent design, flagellar and non-flagellar Type III secretion systems instead provide excellent case studies in the evolution of complex systems from simpler components.

  16. Type III occipital condylar fracture presenting with hydrocephalus, vertebral artery injury and vasospasm: case report

    Energy Technology Data Exchange (ETDEWEB)

    Menendez, J.A.; Baskaya, M.K.; Day, M.A.; Nanda, A. [Dept. of Neurosurgery, Louisiana State Univ., Shreveport (United States); Helath Sciences Center, Shreveport, LA (United States)

    2001-03-01

    Occipital condylar fractures (OCF) are rare and have a high mortality rate. We report a patient with OCF who presented with acute hydrocephalus and died from diffuse vasospasm secondary to vertebral artery injury. A 45-year-old man fell 20 feet from a deer stand and landed on his head. CT showed a type III OCF continuing to the anterior rim of the foramen magnum on the left, with a bone fragment pushing into the medulla, causing hydrocephalus. The patient was stabilized, and a four-vessel arteriogram showed diffuse vasospasm with complete occlusion of the left vertebral artery at the level of the OCF. To our knowledge, this is the first documented case of the conjunction of OCF, hydrocephalus, and vasospasm. (orig.)

  17. The Pseudomonas aeruginosa Type III Translocon Is Required for Biofilm Formation at the Epithelial Barrier

    DEFF Research Database (Denmark)

    Tran, Cindy S; Rangel, Stephanie M; Almblad, Henrik;

    2014-01-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known...... about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates...... a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection....

  18. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    Science.gov (United States)

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy.

  19. The SPI-1-like Type III secretion system: more roles than you think.

    Science.gov (United States)

    Egan, Frank; Barret, Matthieu; O'Gara, Fergal

    2014-01-01

    The type III secretion system (T3SS) is a protein delivery system which is involved in a wide spectrum of interactions, from mutualism to pathogenesis, between Gram negative bacteria and various eukaryotes, including plants, fungi, protozoa and mammals. Various phylogenetic families of the T3SS have been described, including the Salmonella Pathogenicity Island 1 family (SPI-1). The SPI-1 T3SS was initially associated with the virulence of enteric pathogens, but is actually found in a diverse array of bacterial species, where it can play roles in processes as different as symbiotic interactions with insects and colonization of plants. We review the multiple roles of the SPI-1 T3SS and discuss both how these discoveries are changing our perception of the SPI-1 family and what impacts this has on our understanding of the specialization of the T3SS in general.

  20. Diagnosis and Treatment of a Type III Dens Invagination Using Cone-Beam Computed Tomography

    Science.gov (United States)

    Bahmani, Mohsen; Adl, Alireza; Javanmardi, Samane; Naghizadeh, Sina

    2016-01-01

    A 20-year-old man presented with the history of pain and swelling in the anterior maxillary segment. The periapical radiography was indicative of a dental anomaly in right maxillary lateral incisor. Due to the insufficient information from conventional radiography, cone-beam computed tomography (CBCT) was ordered. CBCT showed apical root resorption, large apical lucency and two separate canals with distinct apical foramen (Oehlers type III dens invagination). The CBCT image was used as a guide for dentine removal with an ultrasonic tip. Conventional root canal therapy was done using lateral compaction technique. One-and two-year follow-up radiographies revealed periapical repair and absence of symptoms. PMID:27790268

  1. Dynamics of Langmuir and ion-sound waves in type III solar radio sources

    Science.gov (United States)

    Robinson, P. A.; Willes, A. J.; Cairns, I. H.

    1993-01-01

    The study traces the evolution of Langmuir and ion-sound waves in type III sources, incorporating linear growth, linear damping, and nonlinear electrostatic decay. Improved estimates are obtained for the wavenumber range of growing waves and the nonlinear coupling coefficient for the decay process. It is shown that the conditions in the solar wind do not allow a steady state to be attained; instead, bursty linear and nonlinear interactions take place, consistent with the highly inhomogeneous and impulsive waves actually observed. Nonlinear growth is found to be rapid enough to saturate the growth of the parent Langmuir waves in the available interaction time. The competing processes of nonlinear wave collapse and quasi-linear relaxation are discussed, and it is concluded that neither is responsible for the saturation of Langmuir growth.

  2. Architecture of the major component of the type III secretion system export apparatus.

    Science.gov (United States)

    Abrusci, Patrizia; Vergara-Irigaray, Marta; Johnson, Steven; Beeby, Morgan D; Hendrixson, David R; Roversi, Pietro; Friede, Miriam E; Deane, Janet E; Jensen, Grant J; Tang, Christoph M; Lea, Susan M

    2013-01-01

    Type III secretion systems (T3SSs) are bacterial membrane-embedded nanomachines designed to export specifically targeted proteins from the bacterial cytoplasm. Secretion through T3SS is governed by a subset of inner membrane proteins termed the 'export apparatus'. We show that a key member of the Shigella flexneri export apparatus, MxiA, assembles into a ring essential for secretion in vivo. The ring-forming interfaces are well-conserved in both nonflagellar and flagellar homologs, implying that the ring is an evolutionarily conserved feature in these systems. Electron cryo-tomography revealed a T3SS-associated cytoplasmic torus of size and shape corresponding to those of the MxiA ring aligned to the secretion channel located between the secretion pore and the ATPase complex. This defines the molecular architecture of the dominant component of the export apparatus and allows us to propose a model for the molecular mechanisms controlling secretion.

  3. The immune reponse to type III pneumococcal polysaccharide in mice with malaria.

    Science.gov (United States)

    Wedderburn, N; Dracott, B N

    1977-04-01

    The immune response of BALB/c mice to type III pneumococcal polysaccharide (SIII), as measured by splenic PFC, was abolished at the height of an acute self-limiting attack of malaria caused by the murine plasmodium P. yoelii, over a wide range of antigen doses. The response to antigen, given at various times after clinical recovery, gradually reappeared, but did not reach normal levels until 12 weeks after the injection of the parasite. A second injection of P. yoelii given 1 hr before SIII caused a moderate degree of depression, although in this case the plasmodium does not multiply. In chronic malaria the response to SIII was also very poor. Short term under-nourishment was found to reduce only slightly the response to SIII.

  4. Cross-complementation study of the flagellar type III export apparatus membrane protein FlhB.

    Directory of Open Access Journals (Sweden)

    Clive S Barker

    Full Text Available The bacterial type III export apparatus is found in the flagellum and in the needle complex of some pathogenic Gram-negative bacteria. In the needle complex its function is to secrete effector proteins for infection into Eukaryotic cells. In the bacterial flagellum it exports specific proteins for the building of the flagellum during its assembly. The export apparatus is composed of about five membrane proteins and three soluble proteins. The mechanism of the export apparatus is not fully understood. The five membrane proteins are well conserved and essential. Here a cross-complementation assay was performed: substituting in the flagellar system of Salmonella one of these membrane proteins, FlhB, by the FlhB ortholog from Aquifex aeolicus (an evolutionary distant hyperthermophilic bacteria or a chimeric protein (AquSalFlhB made by the combination of the trans-membrane domain of A. aeolicus FlhB with the cytoplasmic domain of Salmonella FlhB dramatically reduced numbers of flagella and motility. From cells expressing the chimeric AquSalFlhB protein, suppressor mutants with enhanced motility were isolated and the mutations were identified using whole genome sequencing. Gain-of-function mutations were found in the gene encoding FlhA, another membrane protein of the type III export apparatus. Also, mutations were identified in genes encoding 4-hydroxybenzoate octaprenyltransferase, ubiquinone/menaquinone biosynthesis methyltransferase, and 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, which are required for ubiquinone biosynthesis. The mutations were shown by reversed-phase high performance liquid chromatography to reduce the quinone pool of the cytoplasmic membrane. Ubiquinone biosynthesis could be restored for the strain bearing a mutated gene for 4-hydroxybenzoate octaprenyltransferase by the addition of excess exogenous 4-hydroxybenzoate. Restoring the level of ubiquinone reduced flagella biogenesis with the AquSalFlhB chimera

  5. Cross-Complementation Study of the Flagellar Type III Export Apparatus Membrane Protein FlhB

    Science.gov (United States)

    Barker, Clive S.; Samatey, Fadel A.

    2012-01-01

    The bacterial type III export apparatus is found in the flagellum and in the needle complex of some pathogenic Gram-negative bacteria. In the needle complex its function is to secrete effector proteins for infection into Eukaryotic cells. In the bacterial flagellum it exports specific proteins for the building of the flagellum during its assembly. The export apparatus is composed of about five membrane proteins and three soluble proteins. The mechanism of the export apparatus is not fully understood. The five membrane proteins are well conserved and essential. Here a cross-complementation assay was performed: substituting in the flagellar system of Salmonella one of these membrane proteins, FlhB, by the FlhB ortholog from Aquifex aeolicus (an evolutionary distant hyperthermophilic bacteria) or a chimeric protein (AquSalFlhB) made by the combination of the trans-membrane domain of A. aeolicus FlhB with the cytoplasmic domain of Salmonella FlhB dramatically reduced numbers of flagella and motility. From cells expressing the chimeric AquSalFlhB protein, suppressor mutants with enhanced motility were isolated and the mutations were identified using whole genome sequencing. Gain-of-function mutations were found in the gene encoding FlhA, another membrane protein of the type III export apparatus. Also, mutations were identified in genes encoding 4-hydroxybenzoate octaprenyltransferase, ubiquinone/menaquinone biosynthesis methyltransferase, and 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, which are required for ubiquinone biosynthesis. The mutations were shown by reversed-phase high performance liquid chromatography to reduce the quinone pool of the cytoplasmic membrane. Ubiquinone biosynthesis could be restored for the strain bearing a mutated gene for 4-hydroxybenzoate octaprenyltransferase by the addition of excess exogenous 4-hydroxybenzoate. Restoring the level of ubiquinone reduced flagella biogenesis with the AquSalFlhB chimera demonstrating that the

  6. Long-term Outcomes Following Radiotherapy for Adolescent Patients With Nonmetastatic WHO Type III Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Greenwalt, Julie C; Indelicato, Daniel J; Amdur, Robert J; Morris, Christopher G; Kirwan, Jessica M; Mendenhall, William M

    2016-12-01

    To report long-term results of primary radiotherapy for nasopharyngeal cancer (NPC) presenting in the adolescent group. Ten adolescent patients with World Health Organization (WHO) type III NPC were treated with primary radiotherapy at our institution between 1969 and 2007. Median age was 16.5 years (range, 11 to 21). Median radiotherapy dose to the primary target volume was 67.5 Gy (range, 60 to 74.8). The bilateral neck received 51.1 Gy (range, 50 to 60 Gy). Five patients were treated with once-daily radiotherapy and 5 received twice-daily radiotherapy. Three patients received neoadjuvant cisplatin and 5FU, and 1 patient received adjuvant maintenance cisplatin and 5FU. Median follow-up time was 9.5 years (range, 1.94 to 34.74). Fifteen-year overall survival, cause-specific survival, and progression-free survival rates were all 70%. Fifteen-year local and regional control rates were 100% and 90%. One patient recurred regionally and distantly simultaneously, and 2 patients developed distant metastases alone. All 3 died of their disease within 3 years. One patient died from multiple radiation-induced secondary meningiomas 34 years after radiotherapy. Five patients developed hypothyroidism, 3 developed sensorineural hearing loss, and 4 developed dental complications. The overall rates of CTCAE grade 3, 4, and 5 toxicity were 40%, 10%, and 10%, respectively. Despite high-radiation doses to the skull base, none of the patients in this study developed grade 3+ cognitive or vision toxicity. Radiotherapy achieves excellent local control in adolescent patients with unresectable WHO type III NPC. Our data support current protocols to systematically tailor treatment volumes and deescalate radiation doses to reduce treatment toxicity.

  7. Global impact of Salmonella type III secretion effector SteA on host cells

    Energy Technology Data Exchange (ETDEWEB)

    Cardenal-Muñoz, Elena, E-mail: e_cardenal@us.es; Gutiérrez, Gabriel, E-mail: ggpozo@us.es; Ramos-Morales, Francisco, E-mail: framos@us.es

    2014-07-11

    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration.

  8. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.

    Science.gov (United States)

    Schwartz, Daniella M; Bonelli, Michael; Gadina, Massimo; O'Shea, John J

    2016-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.

  9. Type III interferon protects swine against foot-and-mouth disease.

    Science.gov (United States)

    Perez-Martin, Eva; Diaz-San Segundo, Fayna; Weiss, Marcelo; Sturza, Diego F; Dias, Camila C; Ramirez-Medina, Elizabeth; Grubman, Marvin J; de los Santos, Teresa

    2014-10-01

    In recent years, we have developed novel strategies to control foot-and-mouth disease (FMD), including the use of biotherapeutics such as interferons (IFN) delivered by a replication-defective human adenovirus type 5 (Ad5). Swine can be sterilely protected after vaccination with an Ad5 that encodes porcine type I IFN (poIFN-α), and cattle can be similarly protected or develop significantly reduced disease when treated with an Ad5 delivering bovine type III IFN (boIFN-λ3). Here, we have evaluated the efficacy of porcine IFN-λ3 (poIFN-λ3) against FMD virus in vivo. Swine inoculated with different doses of Ad5-poIFN-λ3 were protected against disease in a dose-dependent manner. Despite the absence of systemic antiviral activity, 7 out of 10 Ad5-poIFN-λ3 inoculated animals did not develop disease or viremia, and the other 3 inoculated animals displayed delayed and milder disease by 7 days postchallenge as compared with control animals inoculated with an Ad5 control vector. While analysis of gene expression showed significant induction of IFN and IFN-stimulated genes in Ad5-poIFN-λ3-treated cultured porcine epithelial kidney cells, there was limited gene induction in peripheral blood monocytes isolated from treated swine. These results suggest that treatment with Ad5-poIFN-λ3 is an effective biotherapeutic strategy against FMD in swine.

  10. Planar tetranuclear Dy(III) single-molecule magnet and its Sm(III), Gd(III), and Tb(III) analogues encapsulated by salen-type and β-diketonate ligands.

    Science.gov (United States)

    Yan, Peng-Fei; Lin, Po-Heng; Habib, Fatemah; Aharen, Tomoko; Murugesu, Muralee; Deng, Zhao-Peng; Li, Guang-Ming; Sun, Wen-Bin

    2011-08-01

    The syntheses, structures, and magnetic properties are reported for four new lanthanide clusters [Sm(4)(μ(3)-OH)(2)L(2)(acac)(6)]·4H(2)O (1), [Gd(4)(μ(3)-OH)(2)L(2)(acac)(6)]·4CH(3)CN (2), and [Ln(4)(μ(3)-OH)(2)L(2)(acac)(6)]·2H(2)L·2CH(3)CN (3, Ln = Tb; 4, Ln = Dy) supported by salen-type (H(2)L = N,N'-bis(salicylidene)-1,2-cyclohexanediamine) and β-diketonate (acac = acetylacetonate) ligands. The four clusters were confirmed to be essentially isomorphous by infrared spectroscopy and single-crystal X-ray diffraction. Their crystal structures reveal that the salen-type ligand provides a suitable tetradentate coordination pocket (N(2)O(2)) to encapsulate lanthanide(III) ions. Moreover, the planar Ln(4) core is bridged by two μ(3)-hydroxide, four phenoxide, and two ketonate oxygen atoms. Magnetic properties of all four compounds have been investigated using dc and ac susceptibility measurements. For 4, the static and dynamic data indicate that the Dy(4) complex exhibits slow relaxation of the magnetization below 5 K associated with single-molecule magnet behavior.

  11. Focal adhesion kinase is involved in type III group B streptococcal invasion of human brain microvascular endothelial cells.

    Science.gov (United States)

    Shin, Sooan; Paul-Satyaseela, Maneesh; Maneesh, Paul-Satyaseela; Lee, Jong-Seok; Romer, Lewis H; Kim, Kwang Sik

    2006-01-01

    Group B streptococcus (GBS), the leading cause of neonatal meningitis, has been shown to invade human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. GBS invasion of HBMEC has been shown to require the host cell actin cytoskeleton rearrangements. The present study examined the mechanisms underlying actin cytoskeleton rearrangements that are involved in type III GBS invasion of HBMEC. We showed that type III GBS invasion was inhibited by genistein, a general tyrosine kinase inhibitor (mean 54% invasion decrease at 100 microM), and LY294002, a phosphatidylinositol 3 (PI3) kinase inhibitor (mean 70% invasion decrease at 50 microM), but not by PP2, an inhibitor of the Src family tyrosine kinases. We subsequently showed that the focal adhesion kinase (FAK) was the one of the host proteins tyrosine phosphorylated by type III GBS. Over-expression of a dominant negative form of the FAK C-terminal domain significantly decreased type III GBS invasion of HBMEC (mean 51% invasion decrease). In addition, we showed that FAK phosphorylation correlated with its association of paxillin, an adapter protein of actin filament, and PI3-kinase subunit p85. This is the first demonstration that FAK phosphorylation and its association with paxillin and PI3 kinase play a key role in type III GBS invasion of HBMEC.

  12. Identification of chromosomal genes in Yersinia pestis that influence type III secretion and delivery of Yops into target cells.

    Directory of Open Access Journals (Sweden)

    Andrew S Houppert

    Full Text Available Pathogenic Yersinia species possess a type III secretion system, which is required for the delivery of effector Yop proteins into target cells during infection. Genes encoding the type III secretion machinery, its substrates, and several regulatory proteins all reside on a 70-Kb virulence plasmid. Genes encoded in the chromosome of yersiniae are thought to play important roles in bacterial perception of host environments and in the coordinated activation of the type III secretion pathway. Here, we investigate the contribution of chromosomal genes to the complex regulatory process controlling type III secretion in Yersinia pestis. Using transposon mutagenesis, we identified five chromosomal genes required for expression or secretion of Yops in laboratory media. Four out of the five chromosomal mutants were defective to various extents at injecting Yops into tissue culture cells. Interestingly, we found one mutant that was not able to secrete in vitro but was fully competent for injecting Yops into host cells, suggesting independent mechanisms for activation of the secretion apparatus. When tested in a mouse model of plague disease, three mutants were avirulent, whereas two strains were severely attenuated. Together these results demonstrate the importance of Y. pestis chromosomal genes in the proper function of type III secretion and in the pathogenesis of plague.

  13. Studies on the Painlev\\'e Equations, V, \\\\ Third Painlev\\'e Equations \\\\ of Special Type $P_{\\rm III}(D_7)$ and $P_{\\rm III}(D_8)$

    OpenAIRE

    Ohyama, Yousuke; Kwamuko, Hiroyuki; Sakai, Hidetaka; Okamoto, Kazuo

    2006-01-01

    By means of geometrical classification (\\cite{S}) of space of initial conditions, it is natural to consider the three types, $P_{\\rm III}(D_6)$, $P_{\\rm III}(D_7)$ and $P_{\\rm III}(D_8)$, for the third Painlev\\'e equation. The fourth article of the series of papers \\cite{O2} on the Painlev\\'e equations is concerned with $P_{\\rm III}(D_6)$, generic type of the equation. The other two types, $P_{\\rm III}(D_7)$ and $P_{\\rm III}(D_8)$ are obtained as degeneration from $P_{\\rm III}(D_6...

  14. Identification of a novel PROS1 c.1113T -> GG frameshift mutation in a family with mixed type I/type III protein S deficiency

    NARCIS (Netherlands)

    ten Kate, Min Ki; Mulder, Rene; Platteel, Mathieu; Brouwer, Jan-Leendert P.; van der Steege, Gerrit; van der Meer, Jan

    2006-01-01

    We report a family with type I and type III protein S (PS) deficiency, which showed to be phenotypic variants of the same genetic disease. Direct sequencing analysis of the PROS1 gene was performed to establish the genotype. The ratio of protein C antigen and total PS antigen levels (protein C/S rat

  15. Enhanced expression of the type II transforming growth factor beta receptor in human pancreatic cancer cells without alteration of type III receptor expression.

    Science.gov (United States)

    Friess, H; Yamanaka, Y; Büchler, M; Berger, H G; Kobrin, M S; Baldwin, R L; Korc, M

    1993-06-15

    We have recently found that human pancreatic adenocarcinomas exhibit strong immunostaining for the three mammalian transforming growth factor beta (TGF-beta) isoforms. These important growth-regulating polypeptides bind to a number of proteins, including the type I TGF-beta receptor (T beta R-I), type II TGF-beta receptor (T beta R-II), and the type III TGF-beta receptor (T beta R-III). In the present study we sought to determine whether T beta R-II and T beta R-III expression is altered in pancreatic cancer. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas exhibited a 4.6-fold increase (P beta R-II. In contrast, mRNA levels encoding T beta R-III were not increased. In situ hybridization showed that T beta R-II mRNA was expressed in the majority of cancer cells, whereas mRNA grains encoding T beta R-III were detectable in only a few cancer cells and were present mainly in the surrounding stroma. These findings suggest that enhanced levels of T beta R-II may have a role in regulating human pancreatic cancer cell growth, while T beta R-III may function in the extracellular matrix.

  16. Flare-associated type III radio bursts and dynamics of the EUV jet from SDO/AIA and RHESSI observations

    CERN Document Server

    Chen, Naihwa; Innes, Davina

    2013-01-01

    We present a detailed description of the interrelation between the Type III radio bursts and energetic phenomena associated with the flare activities in Active region AR 11158 at 07:58 UT on 2011, Feb. 15. The timing of the Type-III radio burst measured by the radio wave experiment on the Wind/WAVE and an array of ground-based radio telescopes, coincided with an EUV jet and hard X-ray emission observed by SDO/AIA and RHESSI., respectively. There is clear evidence that the EUV jet shares the same source region as the hard X-ray emission. The temperature of the jet, as determined by multiwavelength measurements of AIA, suggests that type III emission is associated with hot, 7 MK, plasma at the jet's footpoint.

  17. Immunohistochemical expression of types I and III collagen antibodies in the temporomandibular joint disc of human foetuses

    Directory of Open Access Journals (Sweden)

    L.O.C. de Moraes

    2011-07-01

    Full Text Available The objective was to study the morphology of the articular disc and analyse the immunohistochemical expression of types I and III collagen markers in the temporomandibular joint (TMJ disc of human foetuses of different gestational ages. Twenty TMJ from human foetuses supplied by Universidade Federal de Uberaba with gestational ages from 17 to 24 weeks were studied. The gestational age of the foetuses was determined by measuring the crown-rump (CR length. Macroscopically, the foetuses were fixed in 10% formalin solution and dissected by removing the skin and subcutaneous tissue and exposing the deep structures. Immunohistochemical markers of type I and III were used to characterize the existence of collagen fibres. Analysis of the immunohistochemical markers of types I and III collagen revealed the presence of heterotypical fibril networks.

  18. Expression, refolding and spectroscopic characterization of fibronectin type III (FnIII)-homology domains derived from human fibronectin leucine rich transmembrane protein (FLRT)-1,-2, and-3

    DEFF Research Database (Denmark)

    Yang, Lila; Falkesgaard, Maria Hansen; Thulstrup, Peter Waaben

    2017-01-01

    The fibronectin leucine rich transmembrane (FLRT) protein family consists in humans of 3 proteins, FLRT1, -2, and -3. The FLRT proteins contain two extracellular domains separated by an unstructured linker. The most membrane distal part is a leucine rich repeat (LRR) domain responsible for both cis......- and trans-interactions, whereas the membrane proximal part is a fibronectin type III (FnIII) domain responsible for a cis-interaction with members of the fibroblast growth factor receptor 1 (FGFR1) family, which results in FGFR tyrosine kinase activation. Whereas the structures of FLRT LRR domains from...... in inclusion bodies in Escherichia coli. His-tags permitted affinity purification of the domains, which subsequently were refolded on a Ni-NTA agarose column by reducing the concentration of urea. The refolding was confirmed by circular dichroism (CD) and 1H-NMR. By thermal unfolding experiments we show...

  19. Evidence for four- and three-wave interactions in solar type III radio emissions

    Directory of Open Access Journals (Sweden)

    G. Thejappa

    2013-08-01

    Full Text Available The high time resolution observations obtained by the STEREO/WAVES experiment show that in the source regions of solar type III radio bursts, Langmuir waves often occur as intense localized wave packets with short durations of only few ms. One of these wave packets shows that it is a three-dimensional field structure with WLneTe ~ 10−3, where WL is the peak energy density, and ne and Te are the electron density and temperature, respectively. For this wave packet, the conditions of the oscillating two-stream instability (OTSI and supersonic collapse are satisfied within the error range of determination of main parameters. The density cavity, observed during this wave packet indicates that its depth, width and temporal coincidence are consistent with those of a caviton, generated by the ponderomotive force of the collapsing wave packet. The spectrum of each of the parallel and perpendicular components of the wave packet contains a primary peak at fpe, two secondary peaks at fpe ± fS and a low-frequency enhancement below fS, which, as indicated by the frequency and wave number resonance conditions, and the fast Fourier transform (FFT-based tricoherence spectral peak at (fpe, fpe, fpe + fS, fpe − fS, are coupled to each other by the OTSI type of four-wave interaction (fpe is the local electron plasma frequency and fS is the frequency of ion sound waves. In addition to the primary peak at fpe, each of these spectra also contains a peak at 2fpe, which as indicated by the frequency and wave number resonance conditions, and the wavelet-based bicoherence spectral peak at (fpe, fpe, appears to correspond to the second harmonic electromagnetic waves generated as a result of coalescence of oppositely propagating sidebands excited by the OTSI. Thus, these observations for the first time provide combined evidence that (1 the OTSI and related strong turbulence processes play a significant role in the stabilization of the electron beam, (2 the coalescence

  20. Positive regulation of the Hrp type III secretion system in Pseudomonas syringae pv. phaseolicola.

    Science.gov (United States)

    Ortiz-Martín, Inmaculada; Thwaites, Richard; Macho, Alberto P; Mansfield, John W; Beuzón, Carmen R

    2010-05-01

    Disease in compatible hosts and induction of the hypersensitive response in resistant plants by most plant-pathogenic bacteria require a functional type III secretion system (T3SS). Expression of T3SS genes responds to host and environmental factors and is induced within the plant. In Pseudomonas syringae, expression of the T3SS requires HrpL, which is transcriptionally upregulated by HrpR and HrpS. In some pathovars, expression of the hrpRS genes is upregulated by the GacA/S two-component system. Additionally, HrpA, the major component of the T3SS pilus, has also been linked to the regulation of the hrpRS gene expression. Previous studies concerning regulation of hypersensitive response and pathogenesis/hypersensitive response conserved (hrp/hrc) gene expression have used mostly in vitro inducing conditions, different pathovars, and methodology. Here, we analyze the roles of HrpL, GacA, and HrpA in the bean pathogen, using single, double, and triple mutants as well as strains ectopically expressing the regulators. We use real-time polymerase chain reaction analysis in vitro and in planta to quantify gene expression and competitive indices and other assays to assess bacterial fitness. Our results indicate that i) HrpL acts as a general virulence regulator that upregulates non-T3SS virulence determinants and downregulates flagellar function; ii) GacA modulates the expression of hrpL, and its contribution to virulence is entirely HrpL dependent; iii) there is a basal HrpL-independent expression of the T3SS genes in rich medium that is important for full activation of the system, maybe by keeping the system primed for rapid activation upon contact with the plant; and iv) HrpA upregulates expression of the T3SS genes and is essential to activate expression of the hrpZ operon upon contact with the plant.

  1. Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.

    Directory of Open Access Journals (Sweden)

    Hélène Bierne

    Full Text Available Bacterial infections trigger the expression of type I and II interferon genes but little is known about their effect on type III interferon (IFN-λ genes, whose products play important roles in epithelial innate immunity against viruses. Here, we studied the expression of IFN-λ genes in cultured human epithelial cells infected with different pathogenic bacteria and in the mouse placenta infected with Listeria monocytogenes. We first showed that in intestinal LoVo cells, induction of IFN-λ genes by L. monocytogenes required bacterial entry and increased further during the bacterial intracellular phase of infection. Other Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, also induced IFN-λ genes when internalized by LoVo cells. In contrast, Gram-negative bacteria Salmonella enterica serovar Typhimurium, Shigella flexneri and Chlamydia trachomatis did not substantially induce IFN-λ. We also found that IFN-λ genes were up-regulated in A549 lung epithelial cells infected with Mycobacterium tuberculosis and in HepG2 hepatocytes and BeWo trophoblastic cells infected with L. monocytogenes. In a humanized mouse line permissive to fetoplacental listeriosis, IFN-λ2/λ3 mRNA levels were enhanced in placentas infected with L. monocytogenes. In addition, the feto-placental tissue was responsive to IFN-λ2. Together, these results suggest that IFN-λ may be an important modulator of the immune response to Gram-positive intracellular bacteria in epithelial tissues.

  2. [Donation protocol following controlled cardiac death (Maastricht type III donation). First experience].

    Science.gov (United States)

    Rubio-Muñoz, J J; Pérez-Redondo, M; Alcántara-Carmona, S; Lipperheide-Vallhonrat, I; Fernández-Simón, I; Valdivia-de la Fuente, M; Villanueva-Fernández, H; Balandín-Moreno, B; Ortega-López, A; Romera-Ortega, M A; Galdos-Anuncibay, P

    2014-03-01

    To present our experience with the implementation of a donation protocol following controlled cardiac death (Maastricht type III donation). A retrospective descriptive and observational study was made. Intensive Care Unit of a third-level university hospital. Eight patients in an irreversible state, in which withdrawal of all life support had been agreed, were evaluated as potential donors. Application of the adopted protocol. Clinical data of donors, evaluation of a donation protocol following cardiac death, warm ischemia times, and short-term outcome of the recipients. Eight patients were evaluated. In one case donation was not possible because no cardiac arrest developed in the 120 minutes after extubation. The 7 remaining patients were effective kidney donors. Warm ischemia times were less than 23 minutes in all cases. Although 7 of the 14 recipients suffered delayed graft function, all of them achieved good renal function. Donation after cardiac death in patients in an overwhelming and irreversible state represents a potential source of donors not previously considered in this country. The prior development of a consensus-based protocol can help increase the number of organs in combination with those obtained after brain death. In our experience, the results of kidney transplants obtained from donors after cardiac death are good, and the success of these types of protocols could be extended to other organs such as the liver and lungs. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  3. The type III protein secretion system contributes to Xanthomonas citri subsp. citri biofilm formation

    KAUST Repository

    Zimaro, Tamara

    2014-04-18

    Background: Several bacterial plant pathogens colonize their hosts through the secretion of effector proteins by a Type III protein secretion system (T3SS). The role of T3SS in bacterial pathogenesis is well established but whether this system is involved in multicellular processes, such as bacterial biofilm formation has not been elucidated. Here, the phytopathogen Xanthomonas citri subsp. citri (X. citri) was used as a model to gain further insights about the role of the T3SS in biofilm formation. Results: The capacity of biofilm formation of different X. citri T3SS mutants was compared to the wild type strain and it was observed that this secretion system was necessary for this process. Moreover, the T3SS mutants adhered proficiently to leaf surfaces but were impaired in leaf-associated growth. A proteomic study of biofilm cells showed that the lack of the T3SS causes changes in the expression of proteins involved in metabolic processes, energy generation, exopolysaccharide (EPS) production and bacterial motility as well as outer membrane proteins. Furthermore, EPS production and bacterial motility were also altered in the T3SS mutants. Conclusions: Our results indicate a novel role for T3SS in X. citri in the modulation of biofilm formation. Since this process increases X. citri virulence, this study reveals new functions of T3SS in pathogenesis. 2014 Zimaro et al.; licensee BioMed Central Ltd.

  4. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M; Drouet, Christian; Braley, Hal; Nolte, Marc W; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-08-03

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.

  5. AGN III - primordial activity in nuclei of late-type galaxies with pseudobulges

    CERN Document Server

    Komberg, B V

    2013-01-01

    1. Based on observational data on evolution of quasars and galaxies of different types along with the results of numerical simulations we make a conclusion that on low redshifts ($z<0.5$) QSOI/II objects in massive elliptical and spiral galaxies with classical bulges cannot be in late single activity event (be "primordial"). Instead of it they have had events of activity earlier in their evolution. It means that their presence on low redshifts is connected with the recurrence phenomenon, sequential wet minor mergings, because timescale of the activity does not exceed several units of $10^7$ years. 2. We define a new class - "AGN III" as active galactic nuclei in isolated late-type spirals with low-mass rapidly rotating pseudobulges. We also state that only such objects can be in the primordial phase of activity at low redshifts. Black holes in such galaxies have masses $M_{BH}<10^7M_\\odot$ and also, probably very high spin. Such properties can explain their peculiar emission spectra. A good representati...

  6. The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy

    Directory of Open Access Journals (Sweden)

    Janina Bruening

    2017-01-01

    Full Text Available The human interferon (IFN response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs, are an essential component of the innate immune response to hepatitis C virus (HCV. In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses. As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment. In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA exist. Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C.

  7. Adenylate Cyclase Type III Is Not a Ubiquitous Marker for All Primary Cilia during Development

    Science.gov (United States)

    Antal, Maria Cristina; Bénardais, Karelle; Samama, Brigitte; Auger, Cyril; Schini-Kerth, Valérie; Ghandour, Said; Boehm, Nelly

    2017-01-01

    Adenylate cyclase type III (AC3) is localized in plasma membrane of neuronal primary cilium and can be used as a marker of this cilium. AC3 has also been detected in some other primary cilia such as those of fibroblasts, synoviocytes or astrocytes. Despite the presence of a cilium in almost all cell types, we show that AC3 is not a common marker of all primary cilia of different human and mouse tissues during development. In peripheral organs, AC3 is present mainly in primary cilia in cells of the mesenchymal lineage (fibroblasts, chondroblasts, osteoblasts-osteocytes, odontoblasts, muscle cells and endothelial cells). In epithelia, the apical cilium of renal and pancreatic tubules and of ductal plate in liver is AC3-negative whereas the cilium of basal cells of stratified epithelia is AC3-positive. Using fibroblasts cell culture, we show that AC3 appears at the plasma membrane of the primary cilium as soon as this organelle develops. The functional significance of AC3 localization at the cilium membrane in some cells but not others has to be investigated in relationship with cell physiology and expression at the cilium plasma membrane of specific upstream receptors. PMID:28122017

  8. Hijacking of leguminous nodulation signaling by the rhizobial type III secretion system

    Science.gov (United States)

    Okazaki, Shin; Kaneko, Takakazu; Sato, Shusei; Saeki, Kazuhiko

    2013-01-01

    Root–nodule symbiosis between leguminous plants and nitrogen-fixing bacteria (rhizobia) involves molecular communication between the two partners. Key components for the establishment of symbiosis are rhizobium-derived lipochitooligosaccharides (Nod factors; NFs) and their leguminous receptors (NFRs) that initiate nodule development and bacterial entry. Here we demonstrate that the soybean microsymbiont Bradyrhizobium elkanii uses the type III secretion system (T3SS), which is known for its delivery of virulence factors by pathogenic bacteria, to promote symbiosis. Intriguingly, wild-type B. elkanii, but not the T3SS-deficient mutant, was able to form nitrogen-fixing nodules on soybean nfr mutant En1282. Furthermore, even the NF-deficient B. elkanii mutant induced nodules unless T3SS genes were mutated. Transcriptional analysis revealed that expression of the soybean nodulation-specific genes ENOD40 and NIN was increased in the roots of En1282 inoculated with B. elkanii but not with its T3SS mutant, suggesting that T3SS activates host nodulation signaling by bypassing NF recognition. Root-hair curling and infection threads were not observed in the roots of En1282 inoculated with B. elkanii, indicating that T3SS is involved in crack entry or intercellular infection. These findings suggest that B. elkanii has adopted a pathogenic system for activating host symbiosis signaling to promote its infection. PMID:24082124

  9. Feynman Rules in the Type III Natural Flavour-Conserving Two-Higgs Doublet Model

    CERN Document Server

    Lin, C; Yang, Y W; Lin, Chilong; Lee, Chien-er; Yang, Yeou-Wei

    1994-01-01

    We consider a two Higgs-doublet model with $S_3$ symmetry, which implies a $\\pi \\over 2$ rather than 0 relative phase between the vacuum expectation values $$ and $$. The corresponding Feynman rules are derived accordingly and the transformation of the Higgs fields from the weak to the mass eigenstates includes not only an angle rotation but also a phase transformation. In this model, both doublets couple to the same type of fermions and the flavour-changing neutral currents are naturally suppressed. We also demonstrate that the Type III natural flavour-conserving model is valid at tree-level even when an explicit $S_3$ symmetry breaking perturbation is introduced to get a reasonable CKM matrix. In the special case $\\beta = \\alpha$, as the ratio $\\tan\\beta = {v_2 \\over v_1}$ runs from 0 to $\\infty$, the dominant Yukawa coupling will change from the first two generations to the third generation. In the Feynman rules, we also find that the charged Higgs currents are explicitly left-right asymmetric. The ratios ...

  10. Immunohistochemical analysis of type III collagen expression in the lingual mucosa of rats during organogenesis of the tongue.

    Science.gov (United States)

    Iwasaki, Shin-Ichi; Asami, Tomoichiro; Wanichanon, Chaitip; Yoshizawa, Hideki; Aoyagi, Hidekazu

    2008-07-01

    We examined the distribution of immunofluorescence due to immunostaining of type III collagen, differential interference contrast (DIC) images and images obtained in the transmission mode after toluidine blue staining by laser-scanning microscopy of semi-ultrathin sections of epoxy resin-embedded samples, during morphogenesis of the filiform papillae, keratinization of the lingual epithelium, and myogenesis of the rat tongue. Immunoreactivity specific for type III collagen was distributed widely in the mesenchymal connective tissue in fetuses on day 15 after conception (E15), at which time the lingual epithelium was composed of one or two layers of cuboidal cells and the lingual muscle was barely recognizable. Immunoreactivity specific for type III collagen was clearly detected on the lamina propria in fetuses on E17 and E19, and it was relatively distinct just beneath the lingual epithelium. Immunoreactivity specific for type III collagen was sparsely distributed on the connective tissue around the developing lingual muscle. In fetuses on E19, the epithelium became clearly stratified and squamous. At postnatal stages from newborn (P0) to postnatal day 14 (P14), keratinization of the lingual epithelium advanced gradually with the development of filiform papillae. On P0, myogenesis of the tongue was almost completed. The intensity of the fluorescence immunoreactivity specific for type III collagen at postnatal stages was almost same as that on E19. The immunoreactivity around the fully mature muscle was relatively distinct between P0 and P14. Thus, type III collagen appeared in conjunction with the morphogenesis of filiform papillae and the keratinization of the lingual epithelium as well as in the connective tissue that surrounded the lingual muscle during myogenesis of the rat tongue.

  11. Degradation of collagen types I, III, IV and V by extracellular proteinases of an oral flagellate Trichomonas tenax.

    Science.gov (United States)

    Bózner, P; Demes, P

    1991-01-01

    Proteinases secreted by an axenic strain of Trichomonas tenax were active against native types I, III, IV and V collagens when evaluated by polyacrylamide gel electrophoresis. Degradation of all four collagen types was temperature dependent. Basement membrane type IV collagen was digested most effectively. An inhibition of all collagenolytic activities by a specific inhibitor of cysteine proteinases, E-64, and activation by a reducing agent, dithiothreitol, indicated the involvement of cysteine proteinases of the oral flagellate in the cleavage of collagen.

  12. Strains of the Propionibacterium acnes type III lineage are associated with the skin condition progressive macular hypomelanosis

    Science.gov (United States)

    Barnard, Emma; Liu, Jared; Yankova, Eliza; Cavalcanti, Silvana M.; Magalhães, Marcelo; Li, Huiying; Patrick, Sheila; McDowell, Andrew

    2016-01-01

    Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P. acnes isolates recovered from paired lesional and non-lesional skin of PMH patients. Our results demonstrate a strong statistical association between strains from the type III phylogenetic lineage and PMH lesions (P = 0.0019), but not those representing other phylogroups, including those associated with acne (type IA1). We also demonstrate, based on in silico 16S rDNA analysis, that PMH isolates previously recovered from patients in Europe are also consistent with the type III lineage. Using comparative genome analysis, we identified multiple genomic regions that are specific for, or absent from, type III strains compared to other phylogroups. In the former case, these include open reading frames with putative functions in metabolism, transport and transcriptional regulation, as well as predicted proteins of unknown function. Further study of these genomic elements, along with transcriptional and functional analyses, may help to explain why type III strains are associated with PMH. PMID:27555369

  13. Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures—Apropos of Two Cases

    Directory of Open Access Journals (Sweden)

    Hirokazu Takai

    2016-01-01

    Full Text Available Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced Anderson type III fractures with a characteristic fracture pattern that we refer to as “oblique type axis body fracture.” Results. The female patients aged 90 and 72 years, respectively, were both diagnosed with minimally displaced Anderson type III fractures. Both fractures had a characteristic “oblique type” fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1–C3/4 posterior fusion and the course was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion for this injury and suggest early operative stabilization.

  14. Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling

    Science.gov (United States)

    2013-01-01

    Background Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion System), present in the genome of Salmonella typhimurium have been implicated in the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both encoding components of the Type III Secretion System - T3SS) are well understood, T6SS regulation is comparatively less studied. Interestingly, inter-connections among the regulatory elements of these three virulence determinants have also been suggested to be essential for successful infection. However, till date, an integrated view of gene regulation involving the regulators of these three secretion systems and their cross-talk is not available. Results In the current study, relevant regulatory information available from literature have been integrated into a single Boolean network, which portrays the dynamics of T3SS (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory interactions involving a two-component system response regulator YfhA have also been predicted and included in the Boolean network. These predictions are aimed at deciphering the effects of osmolarity on T6SS regulation, an aspect that has been suggested in earlier studies, but the mechanism of which was hitherto unknown. Simulation of the regulatory network was able to recreate in silico the experimentally observed sequential activation of SPI-1, SPI-2 and T6SS. Conclusions The present study integrates relevant gene regulatory data (from literature and our prediction) into a single network, representing the cross-communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of regulatory interactions is expected to improve the current understanding of pathogenesis of S. typhimurium. PMID:24079299

  15. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, C.E.; Taylor, P.E.; Zang, E.A.; Morrison, J.M.; Harley, E.J.; de Cordoba, S.R.; Bacino, C.; Ting, R.C.; Bodner, A.J.; Sarngadharan, M.G.; Gallo, R.C.

    1986-04-25

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men.

  16. Ulysses Observations of Nonlinear Wave-wave Interactions in the Source Regions of Type III Solar Radio Bursts

    Indian Academy of Sciences (India)

    G. Thejappa; R. J. MacDowall

    2000-09-01

    The Ulysses Unified Radio and Plasma Wave Experiment (URAP) has observed Langmuir, ion-acoustic and associated solar type III radio emissions in the interplanetary medium. Bursts of 50-300 Hz (in the spacecraft frame) electric field signals, corresponding to long-wavelength ion-acoustic waves are often observed coincident in time with the most intense Langmuir wave spikes, providing evidence for the electrostatic decay instability. Langmuir waves often occur as envelope solitons, suggesting that strong turbulence processes, such as modulational instability and soliton formation, often coexist with weak turbulence processes, such as electrostatic decay, in a few type III burst source regions.

  17. Investigations into the synthesis and fluorescence properties of Eu(III), Tb(III), Sm(III) and Gd(III) complexes of a novel bis-beta-diketone-type ligand.

    Science.gov (United States)

    Luo, Yi-Ming; Chen, Zhe; Tang, Rui-Ren; Xiao, Lin-Xiang; Peng, Hong-Jian

    2008-02-01

    A novel bis-beta-diketon ligand, 1,1'-(2,6-bispyridyl)bis-3-phenyl-1,3-propane-dione (L), was designed and synthesized and its complexes with Eu(III), Tb(III), Sm(III) and Gd(III) ions were successfully prepared. The ligand and the corresponding metal complexes were characterized by elemental analysis, and infrared, mass and proton nuclear magnetic resonance spectroscopy. Analysis of the IR spectra suggested that each of the lanthanide metal ions coordinated to the ligand via the carbonyl oxygen atoms and the nitrogen atom of the pyridine ring. The fluorescence properties of these complexes in solid state were investigated and it was discovered that all of the lanthanide ions could be sensitized by the ligand (L) to some extent. In particular, the Tb(III) complex was an excellent green-emitter and would be a potential candidate material for applications in organic light-emitting devices (OLEDs) and medical diagnosis.

  18. Investigations into the synthesis and fluorescence properties of Eu(III), Tb(III), Sm(III) and Gd(III) complexes of a novel bis- β-diketone-type ligand

    Science.gov (United States)

    Luo, Yi-Ming; Chen, Zhe; Tang, Rui-Ren; Xiao, Lin-Xiang; Peng, Hong-Jian

    2008-02-01

    A novel bis- β-diketon ligand, 1,1'-(2,6-bispyridyl)bis-3-phenyl-1,3-propane-dione (L), was designed and synthesized and its complexes with Eu(III), Tb(III), Sm(III) and Gd(III) ions were successfully prepared. The ligand and the corresponding metal complexes were characterized by elemental analysis, and infrared, mass and proton nuclear magnetic resonance spectroscopy. Analysis of the IR spectra suggested that each of the lanthanide metal ions coordinated to the ligand via the carbonyl oxygen atoms and the nitrogen atom of the pyridine ring. The fluorescence properties of these complexes in solid state were investigated and it was discovered that all of the lanthanide ions could be sensitized by the ligand (L) to some extent. In particular, the Tb(III) complex was an excellent green-emitter and would be a potential candidate material for applications in organic light-emitting devices (OLEDs) and medical diagnosis.

  19. New tetrachromic VOF stain (Type III-G.S) for normal and pathological fish tissues.

    Science.gov (United States)

    Sarasquete, C; Gutiérrez, M

    2005-01-01

    A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus). In comparison to the original Gutiérrez VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This facilitates the selective staining of different basic tissues and improves the morphological analysis of histochemical approaches of the cell components. The VOF Type III -6.5 stain is composed of a mixture of several dyes of varying size and molecular weight (Orange G

  20. Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm.

    Directory of Open Access Journals (Sweden)

    Alejandro García Castaño

    Full Text Available The p.Ala204Thr mutation (exon 7 of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families were homozygous (57.7% of overall patients. Another 8 patients (5 families were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings presented with the c. -19-?_2053+? del deletion (comprising the entire gene; one patient carried the p.Val170Met mutation (exon 6; and 4 patients (3 siblings presented with the novel p.Glu442Gly mutation (exon 14. On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12 associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16 as well as the already described p.Ala210Val change (exon 7. One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.

  1. IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

    Science.gov (United States)

    Miller, Halie K.; Kwuan, Laura; Schwiesow, Leah; Bernick, David L.; Mettert, Erin; Ramirez, Hector A.; Ragle, James M.; Chan, Patricia P.; Kiley, Patricia J.; Lowe, Todd M.; Auerbuch, Victoria

    2014-01-01

    Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR) was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF. PMID:24945271

  2. Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

    Science.gov (United States)

    García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

    2013-01-01

    The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families. PMID:24058621

  3. USP18-based negative feedback control is induced by type I and type III interferons and specifically inactivates interferon α response.

    Science.gov (United States)

    François-Newton, Véronique; Magno de Freitas Almeida, Gabriel; Payelle-Brogard, Béatrice; Monneron, Danièle; Pichard-Garcia, Lydiane; Piehler, Jacob; Pellegrini, Sandra; Uzé, Gilles

    2011-01-01

    Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy.

  4. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.

    Science.gov (United States)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velde, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2017-01-05

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null. Metabolomics analyses demonstrated a significant concomitant accumulation of the MDH substrate, malate, and fumarate, its immediate precursor in the Krebs cycle, in affected subjects' fibroblasts. Lentiviral complementation with wild-type MDH2 cDNA restored MDH2 levels and mitochondrial MDH activity. Additionally, introduction of the three missense mutations from the affected subjects into Saccharomyces cerevisiae provided functional evidence to support their pathogenicity. Disruption of the Krebs cycle is a hallmark of cancer, and MDH2 has been recently identified as a novel pheochromocytoma and paraganglioma susceptibility gene. We show that loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children.

  5. A modeling study of notch noise responses of type III units in the gerbil dorsal cochlear nucleus.

    Science.gov (United States)

    Zheng, Xiaohan; Voigt, Herbert F

    2006-12-01

    A computational model of the neural circuitry of the gerbil dorsal cochlear nucleus (DCN), based on the MacGregor's neuromime model, was used to simulate type III unit (P-cell) responses to notch noise stimuli. The DCN patch model is based on a previous computational model of the cat DCN [Hancock, K. E., and H. F. Voigt. Ann. Biomed. Eng. 27:73-87, 1999]. According to the experimental study of Parsons et al. [Ann. Biomed. Eng. 29:887-896, 2001], the responses of gerbil DCN type III units to notch noise stimuli are similar to those of cat DCN type IV units, which are thought to be spectral notch detectors. This suggests that type III units in the gerbil DCN may serve as spectral notch detectors. In this modeling study, a simplified notch noise response plot--spike discharge rate vs. notch cutoff frequency plot--was used to compare model responses to the experimental results. Parameter estimation and sensitivity analysis of three connection parameters within the DCN patch have been studied and shows the model is robust, providing reasonable fits to the experimental data from 14 of 15 type III units examined.

  6. In silico identification of potential chaperone genes that belong to type III and type IV secretion systems in Xanthomonas axonopodis pv citri

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    Letícia Khater

    2005-01-01

    Full Text Available The secretion of bacterial virulence factors and flagellar components requires the assistance of specific type III and flagellar chaperones. Standard computational annotation of the genome of Xanthomonas axonopodis pv citri, a plant pathogen that causes citrus canker, initially did not identify any genes belonging to these chaperone categories since the primary sequence homology between them was very low. However, in a search for hypothetical proteins with characteristics similar to these chaperones, we have now identified 30 chromosomal and 10 plasmidial potential genes encoding chaperones belonging to types III/IV, and flagellar secretion systems in this organism. The significance of these findings is discussed.

  7. Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

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    Schiöth Helgi B

    2011-07-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA type I, II and III is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN1. SMN2 is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two SMN2 copies while most SMA type II patients carry three SMN2 copies and SMA III patients have three or four SMN2 copies. The SMN1 gene produces a full-length transcript (FL-SMN while SMN2 is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA. Methods In this study we performed quantification of the SMN2 gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the SMN1 gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker. Results Comparison of the SMN2 copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III and presence of four copies of the SMN2 gene. In both asymptomatic cases we found an increased number of SMN2 copies in the healthy carriers and a biallelic SMN1 absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls. Conclusions We suggest that the SMN2 gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.

  8. Bioinformatics analysis of the locus for enterocyte effacement provides novel insights into type-III secretion

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    Bailey Christopher M

    2005-03-01

    Full Text Available Abstract Background Like many other pathogens, enterohaemorrhagic and enteropathogenic strains of Escherichia coli employ a type-III secretion system to translocate bacterial effector proteins into host cells, where they then disrupt a range of cellular functions. This system is encoded by the locus for enterocyte effacement. Many of the genes within this locus have been assigned names and functions through homology with the better characterised Ysc-Yop system from Yersinia spp. However, the functions and homologies of many LEE genes remain obscure. Results We have performed a fresh bioinformatics analysis of the LEE. Using PSI-BLAST we have been able to identify several novel homologies between LEE-encoded and Ysc-Yop-associated proteins: Orf2/YscE, Orf5/YscL, rORF8/EscI, SepQ/YscQ, SepL/YopN-TyeA, CesD2/LcrR. In addition, we highlight homology between EspA and flagellin, and report many new homologues of the chaperone CesT. Conclusion We conclude that the vast majority of LEE-encoded proteins do indeed possess homologues and that homology data can be used in combination with experimental data to make fresh functional predictions.

  9. The structural and optical properties of type III human collagen biosynthetic corneal substitutes

    Science.gov (United States)

    Hayes, Sally; Lewis, Phillip; Islam, M. Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M.

    2015-01-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2–9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

  10. Cruciate Paralysis in a 20- year -old Male with an Undisplaced Type III Odontoid Fracture.

    Science.gov (United States)

    A, Mansukhani Sameer; V, Tuteja Sanesh; B, Dhar Sanjay

    2016-01-01

    Cruciate Paralysis is a rare incomplete spinal cord syndrome presenting as brachial diplegia with minimal or no involvement of the lower extremities. It occurs as a result of trauma to the cervical spine and is associated with fractures of the axis and/or atlas. Diagnosis is confirmed on MRI and is managed by treatment of the underlying pathology. Prognosis depends on the extent of spinal cord injury and the exact cause. A 20-year-old male presented to the casualty with a history of an injury to the back of the head as a result of a fall. He had severe pain in the neck and shoulder region and experienced difficulty in raising both arms and gripping objects. On examination, he had weakness of both arms, more on the right, involving the C5 to T1 distribution and brisk reflexes. There was no sensory deficit. Radiograph and a computed tomography (CT) scan of the cervical spine showed a type III undisplaced odontoid fracture. MRI showed a signal abnormality in the spinal cord at the level of the cervicomedullary junction extending up to the body of C2 vertebra. The patient was treated with traction in Gardner Wells tongs for six weeks and a sterno-occipital-mandibular immobilizer immobilizer (SOMI) brace thereafter. At three-month follow-up, he had attained complete neurological recovery. Cruciate Paralysis is an important cause of brachial diplegia and must be differentiated from Acute Central Cord syndrome which can have similar clinical features.

  11. Chronic effects of a Salmonella type III secretion effector protein AvrA in vivo.

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    Rong Lu

    Full Text Available BACKGROUND: Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host. METHODS/PRINCIPAL FINDINGS: We infected mice with Salmonella Typhimurium for 27 weeks and investigated the physiological effects as well as the role of AvrA in intestinal inflammation. We found altered body weight, intestinal pathology, and bacterial translocation in spleen, liver, and gallbladder in chronically Salmonella-infected mice. Moreover, AvrA suppressed intestinal inflammation and inhibited the secretion of cytokines IL-12, IFN-gamma, and TNF-alpha. AvrA expression in Salmonella enhanced its invasion ability. Liver abscess and Salmonella translocation in the gallbladder were observed and may be associated with AvrA expression in Salmonella. CONCLUSION/SIGNIFICANCE: We created a mouse model with persistent Salmonella infection in vivo. Our study further emphasizes the importance of the Salmonella effector protein AvrA in intestinal inflammation, bacterial translocation, and chronic infection in vivo.

  12. Structural and Functional Characterization of the Bacterial Type III Secretion Export Apparatus.

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    Tobias Dietsche

    2016-12-01

    Full Text Available Bacterial type III protein secretion systems inject effector proteins into eukaryotic host cells in order to promote survival and colonization of Gram-negative pathogens and symbionts. Secretion across the bacterial cell envelope and injection into host cells is facilitated by a so-called injectisome. Its small hydrophobic export apparatus components SpaP and SpaR were shown to nucleate assembly of the needle complex and to form the central "cup" substructure of a Salmonella Typhimurium secretion system. However, the in vivo placement of these components in the needle complex and their function during the secretion process remained poorly defined. Here we present evidence that a SpaP pentamer forms a 15 Å wide pore and provide a detailed map of SpaP interactions with the export apparatus components SpaQ, SpaR, and SpaS. We further refine the current view of export apparatus assembly, consolidate transmembrane topology models for SpaP and SpaR, and present intimate interactions of the periplasmic domains of SpaP and SpaR with the inner rod protein PrgJ, indicating how export apparatus and needle filament are connected to create a continuous conduit for substrate translocation.

  13. Bile salt receptor complex activates a pathogenic type III secretion system

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

    2016-07-05

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered thatVibrio parahaemolyticusVtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

  14. Use of computed tomography in diagnosis and management of type III dens invaginatus

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    Jayshree Hegde

    2009-01-01

    Full Text Available Background: Dens invaginatus is a developmental malformation, which concerns the non-typical arrangement of dental hard tissues. Conventional diagnostic aids like radiographs play an important role in assessment of complex root canal morphologies. These modalities, however, do not provide detailed information of the complexity as a result of their inherent limitations. This calls for use of more advanced imaging modalities such as computed tomography, which can help the clinician in making a more accurate diagnosis. Report: Type III Dens invaginatus was detected in a 20 year old male patient corresponding to the maxillary lateral incisor and showing extensive periradicular radiolucency and a vestibular sinus. The radiographic and tomographic examination revealed 2 apices: one wide open in the distal part of the root and the other normally formed in the mesial. Treatment plan: Combined non-surgical and surgical endodontic therapy with MTA as a retrograde filling material was planned in this case. Outcome: At follow-up examination after 6 months, the tooth was asymptomatic and radiographically showed repair of the lesion.

  15. The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

    Science.gov (United States)

    McShan, Andrew C.; De Guzman, Roberto N.

    2017-01-01

    Antibiotic resistance in pathogens requires new targets for developing novel antibacterials. The bacterial type III secretion system (T3SS) is an attractive target for developing antibacterials as it is essential in the pathogenesis of many Gram-negative bacteria. The T3SS consists of structural proteins, effectors and chaperones. Over 20 different structural proteins assemble into a complex nanoinjector that punctures a hole on the eukaryotic cell membrane to allow the delivery of effectors directly into the host cell cytoplasm. Defects in the assembly and function of the T3SS render bacteria non-infective. Two major classes of small molecules, salicylidene acylhydrazides and thiazolidinones, have been shown to inhibit multiple genera of bacteria through the T3SS. Many additional chemically and structurally diverse classes of small molecule inhibitors of the T3SS have been identified as well. While specific targets within the T3SS of a few inhibitors have been suggested, the vast majority of specific protein targets within the T3SS remain to be identified or characterized. Other T3SS inhibitors include polymers, proteins and polypeptides mimics. In addition, T3SS activity is regulated by its interaction with biologically relevant molecules, such as bile salts and sterols, which could serve as scaffolds for drug design. PMID:25521643

  16. Type III Effector VopC Mediates Invasion for Vibrio Species

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    Lingling Zhang

    2012-05-01

    Full Text Available Vibrio spp. are associated with infections caused by contaminated food and water. A type III secretion system (T3SS2 is a shared feature of all clinical isolates of V. parahaemolyticus and some V. cholerae strains. Despite its being responsible for enterotoxicity, no molecular mechanism has been determined for the T3SS2-dependent pathogenicity. Here, we show that although Vibrio spp. are typically thought of as extracellular pathogens, the T3SS2 of Vibrio mediates host cell invasion, vacuole formation, and replication of intracellular bacteria. The catalytically active effector VopC is critical for Vibrio T3SS2-mediated invasion. There are other marine bacteria encoding VopC homologs associated with a T3SS; therefore, we predict that these bacteria are also likely to use T3SS-mediated invasion as part of their pathogenesis mechanisms. These findings suggest a new molecular paradigm for Vibrio pathogenicity and modify our view of the roles of T3SS effectors that are translocated during infection.

  17. Phylogeny and virulence of naturally occurring type III secretion system-deficient Pectobacterium strains.

    Science.gov (United States)

    Kim, Hye-Sook; Ma, Bing; Perna, Nicole T; Charkowski, Amy O

    2009-07-01

    Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers.

  18. Phylogeny and Virulence of Naturally Occurring Type III Secretion System-Deficient Pectobacterium Strains▿

    Science.gov (United States)

    Kim, Hye-Sook; Ma, Bing; Perna, Nicole T.; Charkowski, Amy O.

    2009-01-01

    Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers. PMID:19411432

  19. Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.

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    Vincent M Bruno

    2009-08-01

    Full Text Available Recognition of conserved bacterial products by innate immune receptors leads to inflammatory responses that control pathogen spread but that can also result in pathology. Intestinal epithelial cells are exposed to bacterial products and therefore must prevent signaling through innate immune receptors to avoid pathology. However, enteric pathogens are able to stimulate intestinal inflammation. We show here that the enteric pathogen Salmonella Typhimurium can stimulate innate immune responses in cultured epithelial cells by mechanisms that do not involve receptors of the innate immune system. Instead, S. Typhimurium stimulates these responses by delivering through its type III secretion system the bacterial effector proteins SopE, SopE2, and SopB, which in a redundant fashion stimulate Rho-family GTPases leading to the activation of mitogen-activated protein (MAP kinase and NF-kappaB signaling. These observations have implications for the understanding of the mechanisms by which Salmonella Typhimurium induces intestinal inflammation as well as other intestinal inflammatory pathologies.

  20. Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs

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    Teiji Sawa

    2016-10-01

    Full Text Available Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium. In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

  1. Two Higgs Doublet Type III Seesaw with mu-tau symmetry at LHC

    CERN Document Server

    Bandyopadhyay, Priyotosh; Mitra, Manimala

    2009-01-01

    We propose a two Higgs doublet Type III seesaw model with $\\mu$-$\\tau$ flavor symmetry. We add an additional SU(2) Higgs doublet and three SU(2) fermion triplets in our model. The presence of two Higgs doublets allows for natural explanation of small neutrino masses with triplet fermions in the 100 GeV mass range, without fine tuning of the Yukawa couplings to extremely small values. The triplet fermions couple to the gauge bosons and can be thus produced at the LHC. We study in detail the effective cross-sections for the production and subsequent decays of these heavy exotic fermions. We show for the first time that the $\\mu$-$\\tau$ flavor symmetry in the low energy neutrino mass matrix results in mixing matrices for the neutral and charged heavy fermions that are not unity and which carry the flavor symmetry pattern. This flavor structure can be observed in the decays of the heavy fermions at LHC. The large Yukawa couplings in our model result in the decay of the heavy fermions into lighter leptons and Higg...

  2. HpaA from Xanthomonas is a regulator of type III secretion.

    Science.gov (United States)

    Lorenz, Christian; Kirchner, Oliver; Egler, Monique; Stuttmann, Johannes; Bonas, Ulla; Büttner, Daniela

    2008-07-01

    The Gram-negative plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria employs a type III secretion (T3S) system to inject effector proteins into the host cell cytoplasm. Efficient secretion of several effector proteins depends on the cytoplasmic global T3S chaperone HpaB. In this study, we show that HpaB interacts with the virulence factor HpaA, which is secreted by the T3S system and translocated into the plant cell. HpaA promotes secretion of pilus, translocon and effector proteins and therefore appears to be an important control protein of the T3S system. Protein-protein interaction studies and the analysis of HpaA deletion derivatives revealed that the C-terminal protein region, which contains a HpaB binding site, is crucial for the contribution of HpaA to T3S. Secretion of pilus and translocon proteins is not affected when HpaA is expressed as an N-terminal deletion derivative that lacks the secretion and translocation signal. Our data suggest that binding of HpaA to HpaB within the bacterial cell favours secretion of extracellular components of the secretion apparatus. Secretion of HpaA presumably liberates HpaB and thus promotes effector protein secretion after assembly of the T3S apparatus.

  3. Phase Coupling Between Spectral Components of Collapsing Langmuir Solitons in Solar Type III Radio Bursts

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    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    We present the high time resolution observations of one of the Langmuir wave packets obtained in the source region of a solar type III radio burst. This wave packet satisfies the threshold condition of the supersonic modulational instability, as well as the criterion of a collapsing Langmuir soliton, i.e., the spatial scale derived from its peak intensity is less than that derived from its short time scale. The spectrum of t his wave packet contains an intense spectral peak at local electron plasma frequency, f(sub pe) and relatively weaker peaks at 2f(sub pe) and 3f(sub pe). We apply the wavelet based bispectral analysis technique on this wave packet and compute the bicoherence between its spectral components. It is found that the bicoherence exhibits two peaks at (approximately f(sub pe), approximately f(sub pe)) and (approximately f(sub pe) approximately 2f(sub pe)), which strongly suggest that the spectral peak at 2f(sub pe) probably corresponds to the second harmonic radio emission, generated as a result of the merging of antiparallel propagating Langmuir waves trapped in the collapsing Langmuir soliton, and, the spectral peak at 3f(sub pe) probably corresponds to the third harmonic radio emission, generated as a result of merging of a trapped Langmuir wave and a second harmonic electromagnetic wave.

  4. Neutrino Masses at LHC: Minimal Lepton Flavour Violation in Type-III See-saw

    CERN Document Server

    Eboli, O J P; Gonzalez-Garcia, M C

    2011-01-01

    We study the signatures of minimal lepton flavour violation in a simple Type-III see--saw model in which the flavour scale is given by the new fermion triplet mass and it can be naturally light enough to be produced at the LHC. In this model the flavour structure of the couplings of the triplet fermions to the Standard Model leptons can be reconstructed from the neutrino mass matrix and the smallness of the neutrino mass is associated with a tiny violation of total lepton number. Characteristic signatures of this model include suppressed lepton number violation decays of the triplet fermions, absence of displaced vertices in their decays and predictable lepton flavour composition of the states produced in their decays. We study the observability of these signals in the processes $pp\\rightarrow 3\\ell + 2j +\\Sla{E_T}$ and $pp\\rightarrow 2\\ell + 4j$ with $\\ell =e$ or $\\mu$ taking into account the present low energy data on neutrino physics and the corresponding Standard Model backgrounds. Our results indicate th...

  5. /sup 31/P-NMR studies of a case of type III glycogenosis

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    Kawai, Mitsuru; Aizawa, Hitoshi; Itoh, Masamitsu; Yoshikawa, Kohki; Murase, Toshio

    1988-05-01

    /sup 31/P-NMR spectra of skeletal muscles were obtained from a patient of type III glycogenosis (33 y.o. man, reported by one of the authors, T. Murase, in 1973) and the control subject (32 y.o. man), using a superconducting whole body MR (Magnetom, Siemens). Two parameters, 1. muscle pH calculated from the chemical shift of Pi (inorganic phosphate) and PCr (creatine phosphate) and 2. PCr/Pi ratio were monitored before and after the aerobic or ischemic exercise. In resting state, the spectra were normal except for the muscle pH of thigh extensors (7.3), which was obviously higher than that of the control subject (7.0). Significant reduction of PCr/Pi ratio (from 7.0 to 4.1) was observed after the aerobic exercise in thigh extensors. Such a reduction was not recognized in the control subject. The ischemic exercise of forearm muscles revealed slight decrease in muscle pH (from 7.1 to 6.9), which was less prominent than that of the control subject. These results were compatible with the abnormality in the energy metabolism of this disorder, the block in the pathway of glycogenolysis.

  6. Fermentation of Metroxylon sagu resistant starch type III by Lactobacillus sp. and Bifidobacterium bifidum.

    Science.gov (United States)

    Siew-Wai, Loo; Zi-Ni, Tan; Karim, Alias A; Hani, Norziah M; Rosma, Ahmad

    2010-02-24

    The in vitro fermentability of sago (Metroxylon sagu) resistant starch type III (RS(3)) by selected probiotic bacteria was investigated. Sago RS(3) with 12% RS content was prepared by enzymatic debranching of native sago starch with pullulanase enzyme, followed by autoclaving, cooling, and annealing. The fermentation of sago RS(3) by L. acidophilus FTCC 0291, L. bulgaricus FTCC 0411, L. casei FTCC 0442, and B. bifidum BB12 was investigated by observing the bacterial growth, carbohydrate consumption profiles, pH changes, and total short chain fatty acids (SCFA) produced in the fermentation media. Comparisons were made with commercial fructo-oligosaccharide (FOS), Hi-maize 1043, and Hi-maize 240. Submerged fermentations were conducted in 30 mL glass vials for 24 h at 37 degrees C in an oven without shaking. The results indicated that fermentation of sago RS(3) significantly (P < 0.05) yielded the highest count of Lactobacillus sp. accompanied by the largest reduction in pH of the medium. Sago RS(3) was significantly the most consumed substrate compared to FOS and Hi-maizes.

  7. ABNORMAL TYPE-III COLLAGEN PRODUCED BY AN EXON-17-SKIPPING MUTATION OF THE COL3A1 GENE IN EHLERS-DANLOS SYNDROME TYPE-IV IS NOT INCORPORATED INTO THE EXTRACELLULAR-MATRIX

    NARCIS (Netherlands)

    CHIODO, AA; SILLENCE, DO; COLE, WG; BATEMAN, JF

    1995-01-01

    A novel heterozygous mutation of the COL3Al gene that encodes the alpha 1(III) chains of type III collagen was identified in a family with the: acrogeric form of Ehlers-Danlos syndrome type IV (EDS-IV). Cultured dermal fibroblasts produced normal and shortened alpha 1(III) chains. The triple helix o

  8. The cost of virulence: retarded growth of Salmonella Typhimurium cells expressing type III secretion system 1.

    Directory of Open Access Journals (Sweden)

    Alexander Sturm

    2011-07-01

    Full Text Available Virulence factors generally enhance a pathogen's fitness and thereby foster transmission. However, most studies of pathogen fitness have been performed by averaging the phenotypes over large populations. Here, we have analyzed the fitness costs of virulence factor expression by Salmonella enterica subspecies I serovar Typhimurium in simple culture experiments. The type III secretion system ttss-1, a cardinal virulence factor for eliciting Salmonella diarrhea, is expressed by just a fraction of the S. Typhimurium population, yielding a mixture of cells that either express ttss-1 (TTSS-1(+ phenotype or not (TTSS-1(- phenotype. Here, we studied in vitro the TTSS-1(+ phenotype at the single cell level using fluorescent protein reporters. The regulator hilA controlled the fraction of TTSS-1+ individuals and their ttss-1 expression level. Strikingly, cells of the TTSS-1(+ phenotype grew slower than cells of the TTSS-1(- phenotype. The growth retardation was at least partially attributable to the expression of TTSS-1 effector and/or translocon proteins. In spite of this growth penalty, the TTSS-1(+ subpopulation increased from <10% to approx. 60% during the late logarithmic growth phase of an LB batch culture. This was attributable to an increasing initiation rate of ttss-1 expression, in response to environmental cues accumulating during this growth phase, as shown by experimental data and mathematical modeling. Finally, hilA and hilD mutants, which form only fast-growing TTSS-1(- cells, outcompeted wild type S. Typhimurium in mixed cultures. Our data demonstrated that virulence factor expression imposes a growth penalty in a non-host environment. This raises important questions about compensating mechanisms during host infection which ensure successful propagation of the genotype.

  9. The Architecture of the Cytoplasmic Region of Type III Secretion Systems

    Science.gov (United States)

    Makino, Fumiaki; Shen, Dakang; Kajimura, Naoko; Kawamoto, Akihiro; Pissaridou, Panayiota; Oswin, Henry; Pain, Maria; Murillo, Isabel; Namba, Keiichi; Blocker, Ariel J.

    2016-01-01

    Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They mediate injection of protein effectors of virulence from bacteria into eukaryotic host cells to manipulate them during infection. T3SSs involved in virulence (vT3SSs) are evolutionarily related to bacterial flagellar protein export apparatuses (fT3SSs), which are essential for flagellar assembly and cell motility. The structure of the external and transmembrane parts of both fT3SS and vT3SS is increasingly well-defined. However, the arrangement of their cytoplasmic and inner membrane export apparatuses is much less clear. Here we compare the architecture of the cytoplasmic regions of the vT3SSs of Shigella flexneri and the vT3SS and fT3SS of Salmonella enterica serovar Typhimurium at ~5 and ~4 nm resolution using electron cryotomography and subtomogram averaging. We show that the cytoplasmic regions of vT3SSs display conserved six-fold symmetric features including pods, linkers and an ATPase complex, while fT3SSs probably only display six-fold symmetry in their ATPase region. We also identify other morphological differences between vT3SSs and fT3SSs, such as relative disposition of their inner membrane-attached export platform, C-ring/pods and ATPase complex. Finally, using classification, we find that both types of apparatuses can loose elements of their cytoplasmic region, which may therefore be dynamic. PMID:27686865

  10. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    Science.gov (United States)

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

  11. A note on proper affine symmetry in Kantowski-Sachs and Bianchi type III space-times

    CERN Document Server

    Shabbir, Ghulam

    2016-01-01

    We investigate proper affine symmetry for the Kantowski-Sachs and Bianchi type III space-times by using holonomy and decomposability, the rank of the 6X6 Riemann matrix and direct integration techniques. It is shown that the very special classes of the above space-times admit proper affine vector fields.

  12. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via their acti...

  13. A note on classification of proper homothetic vector fields in Kantowski-Sachs and Bianchi type III Lorentzian manifolds

    CERN Document Server

    Shabbir, Ghulam

    2011-01-01

    A complete study of Kantowski-Sachs and Bianchi type III space-times according to their proper homothetic vector fields is given by using direct integration technique. Using the above mentioned technique we have shown that very special classes of the above space-times admit proper homothetic vector fields. The dimension of homothetic vector fields is five.

  14. Virulence determinants of Pseudomonas syringae strains isolated from grasses in the context of a small type III effector repertoire

    DEFF Research Database (Denmark)

    Dudnik, Alexey; Dudler, Robert

    2014-01-01

    Background: Pseudomonas syringae is pathogenic to a large number of plant species. For host colonization and disease progression, strains of this bacterium utilize an array of type III-secreted effectors and other virulence factors, including small secreted molecules such as syringolin A, a pepti...

  15. Periodic solutions of multispecies-competition predator-prey system with Holling's type III functional response and prey supplement

    Directory of Open Access Journals (Sweden)

    Jiwei He

    2007-07-01

    Full Text Available In this paper, we consider a nonautonomous multispecies competition predator-prey system with Holling's type III functional response and prey supplement. It is proved that the system is uniformly persistent under some conditions. Furthermore, we show that the system has a unique positive periodic solution which is globally asymptotically stable.

  16. Talents and Type Iiis: The Effects of the Talents Unlimited Model on Creative Productivity in Gifted Youngsters

    Science.gov (United States)

    Newman, Jane L.

    2005-01-01

    This study examined a set of lessons that integrate the Talents Unlimited Model (TU; C. L. Schlichter, 1986) with the 10 steps of completing a Type III activity (J. S. Renzulli & S. M. Reis, 1985) to determine the effects of these lessons on the quality of students' creative products and on the number of students who completed their products.…

  17. The Low-High-Low Trend of Type III Radio Burst Starting Frequencies and Solar Flare Hard X-rays

    CERN Document Server

    Reid, Hamish A S; Kontar, Eduard P

    2014-01-01

    Using simultaneous X-ray and radio observations from solar flares, we investigate the link between the type III radio burst starting frequency and hard X-ray spectral index. For a proportion of events the relation derived between the starting height (frequency) of type III radio bursts and the electron beam velocity spectral index (deduced from X-rays) is used to infer the spatial properties (height and size) of the electron beam acceleration region. Both quantities can be related to the distance travelled before an electron beam becomes unstable to Langmuir waves. To obtain a list of suitable events we considered the RHESSI catalogue of X-ray flares and the Phoenix 2 catalogue of type III radio bursts. From the 200 events that showed both type III and X-ray signatures, we selected 30 events which had simultaneous emission in both wavelengths, good signal to noise in the X-ray domain and > 20 seconds duration. We find that > 50 % of the selected events show a good correlation between the starting frequencies ...

  18. Structure and Activity of the RNA-Targeting Type III-B CRISPR-Cas Complex of Thermus thermophilus

    NARCIS (Netherlands)

    Staals, R.H.J.; Agari, Y.; Maki-Yonekura, S.; Zhu, Y.; Taylor, D.W.; van Duijn, E.; Barendregt, A.; Vlot, M.C.; Koehorst, J.J.; Sakamoto, K.; Masuda, A.; Dohmae, N.; Schaap, P.J.; Doudna, J.A.; Heck, A.J.R.; Yonekura, K.; van der Oost, J.; Shinkai, A.

    2013-01-01

    The CRISPR-Cas system is a prokaryotic host defense system against genetic elements. The Type III-B CRISPR-Cas system of the bacterium Thermus thermophilus, the TtCmr complex, is composed of six different protein subunits (Cmr1-6) and one crRNA with a stoichiometry of Cmr112131445361:crRNA1. The TtC

  19. Adsorption of As(III) from Aqueous Solutions by Novel Fe-Mg Type Hydrotalcite.

    Science.gov (United States)

    Ogata, Fumihiko; Kawasaki, Naohito

    2015-01-01

    Morphological and chemical evaluation of Fe-Mg hydrotalcite (Fe-HT) was performed using scanning electron microscopy, X-ray diffraction analysis, and electron microanalysis for application as an adsorbent for water treatment. The adsorption of arsenic III (As(III)) on Fe-HT was evaluated via examination of the effect of the contact time and analysis of the adsorption isotherm. The amount of As(III) adsorbed increased slightly with increasing temperature. The results of the adsorption isotherm studies suggested that As(III) adsorption can be well described by both the Freundlich and Langmuir equations. The adsorption of As(III) on Fe-HT reached equilibrium within 24 h, and the adsorption kinetic data fit the pseudo-second-order kinetic model better than the pseudo-first-order model. The amount of As(III) present on the surface of Fe-HT increased after As(III) adsorption, and the crystalline structure of Fe-HT was maintained after adsorption of As(III). The (003) and (006) peaks in the X-ray diffraction patterns were attributed to basal reflections, and these peaks shifted from respective 2θ values of 10.86 and 21.94° to 11.12 and 22.52°, indicating exchange of As(III) with chloride ions in Fe-HT with consequent narrowing of the inter-layer spacing. Collectively, these results suggest that Fe-HT is prospectively useful for the adsorption of As(III) from aqueous solutions.

  20. Glucocorticoids inhibit the synthesis rate of type III collagen, but do not affect the hepatic clearance of its aminoterminal propeptide (PIIINP)

    DEFF Research Database (Denmark)

    Hansen, M; Stoltenberg, M; Høst, N B;

    1995-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen metabolism. The serum concentration of PIIINP is increased during inflammation, probably reflecting stimulated biosynthesis of type III collagen. Serum PIIINP decreases during glucocorticoid treatment....... This has been interpreted as an inhibited biosynthesis of type III collagen. However, circulating PIIINP is extracted by the liver, and the decrease in serum PIIINP may also be caused by an increased hepatic elimination. In the present study we investigated the influence of intravenous methylprednisolone...

  1. Spatiotemporal Patterns of a Predator-Prey System with an Allee Effect and Holling Type III Functional Response

    Science.gov (United States)

    Li, Yuanyuan; Wang, Jinfeng

    A diffusive Gause type predator-prey system with Allee effect in prey growth and Holling type III response subject to Neumann boundary conditions is investigated. Existence of nonconstant positive steady state solutions is proved by Leray-Schauder degree theory and bifurcation theory. Global stability of the positive equilibrium of the system is also investigated. Moreover, bifurcations of spatially homogeneous and nonhomogeneous periodic solutions are analyzed. Our rigorous results justify some recent ecological observations.

  2. Manganese(III)-containing Wells-Dawson sandwich-type polyoxometalates: comparison with their manganese(II) counterparts.

    Science.gov (United States)

    Lebrini, Mounim; Mbomekallé, Israël M; Dolbecq, Anne; Marrot, Jérôme; Berthet, Patrick; Ntienoue, Joseline; Sécheresse, Francis; Vigneron, Jacky; Etcheberry, Arnaud

    2011-07-18

    We present the synthesis and structural characterization, assessed by various techniques (FTIR, TGA, UV-vis, elemental analysis, single-crystal X-ray diffraction for three compounds, magnetic susceptibility, and electrochemistry) of five manganese-containing Wells-Dawson sandwich-type (WDST) complexes. The dimanganese(II)-containing complex, [Na(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](18-) (1), was obtained by reaction of MnCl(2) with 1 equiv of [As(2)W(15)O(56)](12-) in acetate medium (pH 4.7). Oxidation of 1 by Na(2)S(2)O(8) in aqueous solution led to the dimanganese(III) complex [Na(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](16-) (2), while its trimanganese(II) homologue, [Na(H(2)O)(2)Mn(II)(H(2)O)Mn(II)(2)(As(2)W(15)O(56))(2)](17-) (3), was obtained by addition of ca. 1 equiv of MnCl(2) to a solution of 1 in 1 M NaCl. The trimanganese(III) and tetramanganese(III) counterparts, [Mn(III)(H(2)O)Mn(III)(2)(As(2)W(15)O(56))(2)](15-) (4) and [Mn(III)(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](12-) (6), are, respectively, obtained by oxidation of aqueous solutions of 3 and [Mn(II)(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](16-) (5) by Na(2)S(2)O(8). Single-crystal X-ray analyses were carried out on 2, 3, and 4. BVS calculations and XPS confirmed that the oxidation state of Mn centers is +II for complexes 1, 3, and 5 and +III for 2, 4, and 6. A complete comparative electrochemical study was carried out on the six compounds cited above, and it was possible to observe the distinct redox steps Mn(IV/III) and Mn(III/II). Magnetization measurements, as a function of temperature, confirm the presence of antiferromagnetic interactions between the Mn ions in these compounds in all cases with the exception of compound 2.

  3. Gartland types IIB and III supracondylar fractures of the humerus in children: is Blount's method effective and safe?

    Science.gov (United States)

    Pham, Thuy-Trang; Accadbled, Franck; Abid, Abdelaziz; Ibnoulkhatib, Aissa; Bayle-Iniguez, Xavier; Wargny, Matthieu; Sales de Gauzy, Jérôme

    2017-07-20

    Blount's method is controversial for the treatment of Gartland types IIB and III supracondylar fracture of the humerus (SCFH) in children. The purpose of this study was to evaluate the clinical and radiologic outcomes and the failure and complication rates. All types IIB and III SCFH treated with Blount's method from 2003-2013 were included in this retrospective single-center study. Clinical assessment was performed according to Flynn criteria. Baumann angle, anteversion angle, anterior humeral line, and humeroulnar angle were measured for radiographic assessment. Among 447 children with types IIB and III SCHF, 339 were treated according to Blount's method. There were 173 boys (51%), and the mean age was 6.3 years (1-14 years); 71% were type III. Mean time to surgery was 5.7 hours. According to Flynn criteria, results were satisfactory in 91% of cases. No compartment syndrome was encountered. There were 16 (4.7%) secondary displacements requiring surgical revision. Five (1.9%) children developed a cubitus varus deformity. At latest follow-up, the mean Baumann angle was 74.7° (95% confidence interval, 74.1-75.3), the mean anteversion angle was 39.9° (95% confidence interval, 39.5-40.3), the anterior humeral line was normal in 87.6% of cases, and the mean humeroulnar angle was 8.7°. Blount's method is appropriate to manage types IIB and III SCFH, provided anatomic and stable reduction is obtained. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  4. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Danielle Cristina Tomaz da [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Lima-Leopoldo, Ana Paula; Leopoldo, André Soares [Departamento de Esportes, Centro de Educação Física e Desportos da Universidade Federal do Espírito Santo (UFES), Vitória, ES (Brazil); Campos, Dijon Henrique Salomé de; Nascimento, André Ferreira do [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Oliveira, Sílvio Assis Junior de [Escola de Fisioterapia da Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil); Padovani, Carlos Roberto [Departamento de Bioestatística do Instituto de Ciências Biológicas da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Cicogna, Antonio Carlos, E-mail: dany.tomaz@gmail.com [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-02-15

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C{sub 15} and Ob{sub 15}) and 30 (C{sub 30} and Ob{sub 30}) consecutive weeks. Obesity was determined by adiposity index. The Ob{sub 15} group was similar to the C{sub 15} group regarding the expression of myocardial collagen type I; however, expression in the Ob{sub 30} group was less than C{sub 30} group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob{sub 30} when compared with Ob{sub 15}. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression.

  5. An N-terminal three-helix fragment of the exchangeable insect apolipoprotein apolipophorin III conserves the lipid binding properties of wild-type protein.

    Science.gov (United States)

    Dettloff, M; Weers, P M; Niere, M; Kay, C M; Ryan, R O; Wiesner, A

    2001-03-13

    Apolipophorin III (apoLp-III) from the greater wax moth Galleria mellonella is an exchangeable insect apolipoprotein that consists of five amphipathic alpha-helices, sharing high sequence identity with apoLp-III from the sphinx moth Manduca sexta whose structure is available. To define the minimal requirement for apoLp-III structural stability and function, a C-terminal truncated apoLp-III encompassing residues 1-91 of this 163 amino acid protein was designed. Far-UV circular dichroism spectroscopy revealed apoLp-III(1-91) has 50% alpha-helix secondary structure content in buffer (wild-type apoLp-III 86%), increasing to essentially 100% upon interactions with dimyristoylphosphatidylcholine (DMPC). Guanidine hydrochloride denaturation studies revealed similar stability properties for wild-type apoLp-III and apoLp-III(1-91). Resistance to denaturation for both proteins increased substantially upon association with phospholipid. In the absence of lipid, wild-type apoLp-III was monomeric whereas apoLp-III(1-91) partly formed dimers and trimers. Discoidal apoLp-III(1-91)-DMPC complexes were smaller in diameter (13.5 nm) compared to wild-type apoLp-III (17.7 nm), and more molecules of apoLp-III(1-91) associated with the complexes. Lipid interaction revealed that apoLp-III(1-91) binds to modified spherical lipoprotein surfaces and efficiently transforms phospholipid vesicles into discoidal complexes. Thus, the first three helices of G. mellonella apoLp-III contain the basic features required for maintenance of the structural integrity of the entire protein.

  6. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Using Microwave Type-III Pairs

    Science.gov (United States)

    Tan, B. L.; Karlický, M.; Mészárosová, H.; Kashapova, L.; Huang, J.; Yan, Y.; Kontar, E. P.

    2016-10-01

    We report a peculiar and interesting train of microwave Type-III pair bursts in the impulsive rising phase of a solar flare on 26 September 2011. The observations include radio spectrometers at frequencies of 0.80 - 2.00 GHz from the Ondřejov radiospectrograph in the Czech Republic (ORSC), hard X-ray from the Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) and Gamma-Ray Burst Monitor onboard the Fermi Space Telescope ( Fermi/GRB), EUV images from the Sun Watcher using APS detectors and image Processing instrument onboard the Project for Onboard Autonomy 2 (SWAP/PROBA2), and magnetograms from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory (SDO/HMI). By using a recently developed method (Tan et al., Res. Astron. Astrophys. 16, 82, 2016a), we diagnosed the plasma density, temperature, plasma-β, magnetic field near the source region, the energy of energetic electrons, and the distance between the acceleration region and the emission start sites of Type-III bursts. From the diagnostics, we find that i) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites have almost no obvious variations during the period of Type-III pair trains, while the energy of electrons has an obvious peak value that is consistent with the hard X-ray emission. ii) The plasma-β is much higher than unity, showing a highly dynamic process near the emission start site of Type-III bursts. iii) Although the reversed-slope Type-III branches drift more slowly by one order of magnitude than that of the normal Type-IIIs, the related descending and ascending electrons still could have energy of the same order of magnitude. These facts indicate that both the ascending and descending electrons are possibly accelerated by a similar mechanism and in a small source region. These diagnostics can help us to understand the physics in the source region of solar bursts.

  7. Tracking the cognitive, social and neuroanatomical profile in early neurodegeneration: Type III Cockayne syndrome

    Directory of Open Access Journals (Sweden)

    Sandra eBaez

    2013-11-01

    Full Text Available Cockayne syndrome (CS is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind and empathy tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions, which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.

  8. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus.

    Science.gov (United States)

    Zhao, Yue; Yang, Jieling; Shi, Jianjin; Gong, Yi-Nan; Lu, Qiuhe; Xu, Hao; Liu, Liping; Shao, Feng

    2011-09-14

    Inflammasomes are large cytoplasmic complexes that sense microbial infections/danger molecules and induce caspase-1 activation-dependent cytokine production and macrophage inflammatory death. The inflammasome assembled by the NOD-like receptor (NLR) protein NLRC4 responds to bacterial flagellin and a conserved type III secretion system (TTSS) rod component. How the NLRC4 inflammasome detects the two bacterial products and the molecular mechanism of NLRC4 inflammasome activation are not understood. Here we show that NAIP5, a BIR-domain NLR protein required for Legionella pneumophila replication in mouse macrophages, is a universal component of the flagellin-NLRC4 pathway. NAIP5 directly and specifically interacted with flagellin, which determined the inflammasome-stimulation activities of different bacterial flagellins. NAIP5 engagement by flagellin promoted a physical NAIP5-NLRC4 association, rendering full reconstitution of a flagellin-responsive NLRC4 inflammasome in non-macrophage cells. The related NAIP2 functioned analogously to NAIP5, serving as a specific inflammasome receptor for TTSS rod proteins such as Salmonella PrgJ and Burkholderia BsaK. Genetic analysis of Chromobacterium violaceum infection revealed that the TTSS needle protein CprI can stimulate NLRC4 inflammasome activation in human macrophages. Similarly, CprI is specifically recognized by human NAIP, the sole NAIP family member in human. The finding that NAIP proteins are inflammasome receptors for bacterial flagellin and TTSS apparatus components further predicts that the remaining NAIP family members may recognize other unidentified microbial products to activate NLRC4 inflammasome-mediated innate immunity. © 2011 Macmillan Publishers Limited. All rights reserved

  9. Potassium transport of Salmonella is important for type III secretion and pathogenesis.

    Science.gov (United States)

    Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C; Lu, Sangwei

    2013-08-01

    Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K(+)), sodium ion (Na(+)) and proton (H(+)) are involved in nearly all aspects of bacterial growth and survival. K(+) is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K(+) transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K(+) transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K(+) transport through deletion of K(+) transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K(+) transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K(+) transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria.

  10. Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome.

    Science.gov (United States)

    Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres

    2013-01-01

    Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor's brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.

  11. The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi.

    Science.gov (United States)

    Johnson, Rebecca; Byrne, Alexander; Berger, Cedric N; Klemm, Elizabeth; Crepin, Valerie F; Dougan, Gordon; Frankel, Gad

    2017-02-15

    Strains of the various Salmonella enterica serovars cause gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (Salmonella pathogenicity island 1 [SPI-1] and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton postinfection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S. enterica serovar Typhimurium and S Typhi; direct comparison of the protein sequences revealed that S Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S Typhi and S. Typhimurium strains demonstrated that, unlike SptP in S. Typhimurium, SptP in S Typhi was not involved in invasion or cytoskeletal recovery postinfection. Investigation of whether the observed amino acid changes within SptP of S Typhi affected its function revealed that S Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that while S. Typhimurium SptP is stable intracellularly within S Typhi, S Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S. Typhimurium. Direct assessment of the strength of the interaction between SptP and SicP of both serovars via bacterial two-hybrid analysis demonstrated that S Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S. Typhimurium. Taken together, our results suggest that changes within the chaperone-binding domain of SptP in S Typhi hinder binding to its chaperone, resulting in instability, preventing translocation, and therefore restricting the intracellular activity of this effector.

  12. Characteristics of Metroxylon sagu resistant starch type III as prebiotic substance.

    Science.gov (United States)

    Zi-Ni, Tan; Rosma, Ahmad; Napisah, Hussin; Karim, Alias A; Liong, Min-Tze

    2015-04-01

    Resistant starch type III (RS3 ) was produced from sago (Metroxylon sagu) and evaluated for its characteristics as a prebiotic. Two RS3 samples designated sago RS and HCl-sago RS contained 35.71% and 68.30% RS, respectively, were subjected to hydrolyses by gastric juice and digestive enzymes and to absorption. Both sago RS and HCl-sago RS were resistant to 180 min hydrolysis by gastric acidity at pH 1 to 4 with less than 0.85% hydrolyzed. Both samples were also resistant toward hydrolysis by gastrointestinal tract enzymes and intestinal absorption with 96.75% and 98.69% of RS3 were recovered respectively after 3.5 h digestion and overnight dialysis at 37 °C. Sago RS3 supported the growth of both beneficial (lactobacilli and Bifidobacteria) and pathogenic microbes (Escherichia coli, Campylobacter coli, and Clostridium perfringens) in the range of 2.60 to 3.91 log10 CFU/mL. Hence, prebiotic activity score was applied to describe the extent to which sago RS3 supports selective growth of the lactobacilli and bifidobacteria strains over pathogenic bacteria. The highest scores were obtained from Bifidobacterium sp. FTDC8943 grown on sago RS (+0.26) and HCl-sago RS (+0.24) followed by L. bulgaricus FTDC1511 grown on sago RS (+0.21). The findings had suggested that sago RS3 has the prebiotic partial characteristics and it is suggested to further assess the suitability of sago RS3 as a prebiotic material.

  13. Fibronectin unfolding revisited: modeling cell traction-mediated unfolding of the tenth type-III repeat.

    Directory of Open Access Journals (Sweden)

    Elaine P S Gee

    Full Text Available Fibronectin polymerization is essential for the development and repair of the extracellular matrix. Consequently, deciphering the mechanism of fibronectin fibril formation is of immense interest. Fibronectin fibrillogenesis is driven by cell-traction forces that mechanically unfold particular modules within fibronectin. Previously, mechanical unfolding of fibronectin has been modeled by applying tensile forces at the N- and C-termini of fibronectin domains; however, physiological loading is likely focused on the solvent-exposed RGD loop in the 10(th type-III repeat of fibronectin (10FNIII, which mediates binding to cell-surface integrin receptors. In this work we used steered molecular dynamics to study the mechanical unfolding of 10FNIII under tensile force applied at this RGD site. We demonstrate that mechanically unfolding 10FNIII by pulling at the RGD site requires less work than unfolding by pulling at the N- and C- termini. Moreover, pulling at the N- and C-termini leads to 10FNIII unfolding along several pathways while pulling on the RGD site leads to a single exclusive unfolding pathway that includes a partially unfolded intermediate with exposed hydrophobic N-terminal beta-strands - residues that may facilitate fibronectin self-association. Additional mechanical unfolding triggers an essential arginine residue, which is required for high affinity binding to integrins, to move to a position far from the integrin binding site. This cell traction-induced conformational change may promote cell detachment after important partially unfolded kinetic intermediates are formed. These data suggest a novel mechanism that explains how cell-mediated forces promote fibronectin fibrillogenesis and how cell surface integrins detach from newly forming fibrils. This process enables cells to bind and unfold additional fibronectin modules - a method that propagates matrix assembly.

  14. Pseudomonas syringae pv. phaseolicola Mutants Compromised for type III secretion system gene induction.

    Science.gov (United States)

    Deng, Xin; Xiao, Yanmei; Lan, Lefu; Zhou, Jian-Min; Tang, Xiaoyan

    2009-08-01

    Pseudomonas syringae bacteria utilize the type III secretion system (T3SS) to deliver effector proteins into host cells. The T3SS and T3 effector genes (together called the T3 genes hereafter) are repressed in nutrient-rich medium but rapidly induced after the bacteria are transferred into minimal medium or infiltrated into plants. The induction of the T3 genes is mediated by HrpL, an alternative sigma factor that recognizes the conserved hrp box motif in the T3 gene promoters. The induction of hrpL is mediated by HrpR and HrpS, two homologous proteins that bind the hrpL promoter. To identify additional genes involved in regulation of the T3 genes, we screened for the P. syringae pv. phaseolicola NPS3121 transposon-tagged mutants with reduced induction of avrPto-luc and hrpL-luc, reporter genes for promoters of effector gene avrPto and hrpL, respectively. Determination of the transposon-insertion sites revealed genes with putative functions in signal transduction and transcriptional regulation, protein synthesis, and basic metabolism. A transcriptional regulator (AefR(NPS3121)) was identified in our screen that is homologous to AefR of P. syringae pv. syringae strain B728a, a regulator of the quorum-sensing signal and epiphytic traits, but was not known to regulate the T3 genes. AefR(NPS3121) in P. syringae pv. phaseolicola NPS3121 and AefR in P. syringae pv. syringae B728a behave similarly in regulating the quorum-sensing signal in liquid medium but differ in regulating the epiphytic traits, including swarming motility, leaf entry, and epiphytic survival.

  15. The Type III Secretion System-Related CPn0809 from Chlamydia pneumoniae.

    Directory of Open Access Journals (Sweden)

    Astrid C Engel

    Full Text Available Chlamydia pneumoniae is an intracellular Gram-negative bacterium that possesses a type III secretion system (T3SS, which enables the pathogen to deliver, in a single step, effector proteins for modulation of host-cell functions into the human host cell cytosol to establish a unique intracellular niche for replication. The translocon proteins located at the top of the T3SS needle filament are essential for its function, as they form pores in the host-cell membrane. Interestingly, unlike other Gram-negative bacteria, C. pneumoniae has two putative translocon operons, named LcrH_1 and LcrH_2. However, little is known about chlamydial translocon proteins. In this study, we analyzed CPn0809, one of the putative hydrophobic translocators encoded by the LcrH_1 operon, and identified an 'SseC-like family' domain characteristic of T3S translocators. Using bright-field and confocal microscopy, we found that CPn0809 is associated with EBs during early and very late phases of a C. pneumoniae infection. Furthermore, CPn0809 forms oligomers, and interacts with the T3SS chaperone LcrH_1, via its N-terminal segment. Moreover, expression of full-length CPn0809 in the heterologous host Escherichia coli causes a grave cytotoxic effect that leads to cell death. Taken together, our data indicate that CPn0809 likely represents one of the translocon proteins of the C. pneumoniae T3SS, and possibly plays a role in the translocation of effector proteins in the early stages of infection.

  16. Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn and preschool children. A systematic review.

    Science.gov (United States)

    Sinikumpu, Juha-Jaakko; Ojaniemi, Marja; Lehenkari, Petri; Serlo, Willy

    2015-08-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders, of which Type III is the most severe among survivors. The disease is characterised in particular by bone fragility, decreased bone mass and increased incidence of fractures. Other usual findings are muscle hypotonia, joint hypermobility and short stature. Fractures and weak bones may consequently cause limb and spinal deformity and chronic physical disability. Bisphosphonates have revolutionised the treatment of newborn children with severe OI type III. Surgery is still needed in most patients due to high frequency of the fractures. In this systematic review we describe the present state-of-art in treating the most severe type of OI in newborn and preschool children with their bone fractures.

  17. Heterologous gene expression and functional analysis of a type III polyketide synthase from Aspergillus niger NRRL 328

    Energy Technology Data Exchange (ETDEWEB)

    Kirimura, Kohtaro, E-mail: kkohtaro@waseda.jp; Watanabe, Shotaro; Kobayashi, Keiichi

    2016-05-13

    Type III polyketide synthases (PKSs) catalyze the formation of pyrone- and resorcinol-types aromatic polyketides. The genomic analysis of the filamentous fungus Aspergillus niger NRRL 328 revealed that this strain has a putative gene (chr-8-2: 2978617–2979847) encoding a type III PKS, although its functions are unknown. In this study, for functional analysis of this putative type III PKS designated as An-CsyA, cloning and heterologous expression of the An-CsyA gene (An-csyA) in Escherichia coli were performed. Recombinant His-tagged An-CsyA was successfully expressed in E. coli BL21 (DE3), purified by Ni{sup 2+}-affinity chromatography, and used for in vitro assay. Tests on the substrate specificity of the His-tagged An-CsyA with myriad acyl-CoAs as starter substrates and malonyl-CoA as extender substrate showed that His-tagged An-CsyA accepted fatty acyl-CoAs (C2-C14) and produced triketide pyrones (C2-C14), tetraketide pyrones (C2-C10), and pentaketide resorcinols (C10-C14). Furthermore, acetoacetyl-CoA, malonyl-CoA, isobutyryl-CoA, and benzoyl-CoA were also accepted as starter substrates, and both of triketide pyrones and tetraketide pyrones were produced. It is noteworthy that the His-tagged An-CsyA produced polyketides from malonyl-CoA as starter and extender substrates and produced tetraketide pyrones from short-chain fatty acyl-CoAs as starter substrates. Therefore, this is the first report showing the functional properties of An-CsyA different from those of other fungal type III PKSs. -- Highlights: •Type III PKS from Aspergillus niger NRRL 328, An-CsyA, was cloned and characterized. •An-CsyA produced triketide pyrones, tetraketide pyrones and pentaketide resorcinols. •Functional properties of An-CsyA differs from those of other fungal type III PKSs.

  18. Assembly and stoichiometry of the core structure of the bacterial flagellar type III export gate complex.

    Science.gov (United States)

    Fukumura, Takuma; Makino, Fumiaki; Dietsche, Tobias; Kinoshita, Miki; Kato, Takayuki; Wagner, Samuel; Namba, Keiichi; Imada, Katsumi; Minamino, Tohru

    2017-08-01

    The bacterial flagellar type III export apparatus, which is required for flagellar assembly beyond the cell membranes, consists of a transmembrane export gate complex and a cytoplasmic ATPase complex. FlhA, FlhB, FliP, FliQ, and FliR form the gate complex inside the basal body MS ring, although FliO is required for efficient export gate formation in Salmonella enterica. However, it remains unknown how they form the gate complex. Here we report that FliP forms a homohexameric ring with a diameter of 10 nm. Alanine substitutions of conserved Phe-137, Phe-150, and Glu-178 residues in the periplasmic domain of FliP (FliPP) inhibited FliP6 ring formation, suppressing flagellar protein export. FliO formed a 5-nm ring structure with 3 clamp-like structures that bind to the FliP6 ring. The crystal structure of FliPP derived from Thermotoga maritia, and structure-based photo-crosslinking experiments revealed that Phe-150 and Ser-156 of FliPP are involved in the FliP-FliP interactions and that Phe-150, Arg-152, Ser-156, and Pro-158 are responsible for the FliP-FliO interactions. Overexpression of FliP restored motility of a ∆fliO mutant to the wild-type level, suggesting that the FliP6 ring is a functional unit in the export gate complex and that FliO is not part of the final gate structure. Copurification assays revealed that FlhA, FlhB, FliQ, and FliR are associated with the FliO/FliP complex. We propose that the assembly of the export gate complex begins with FliP6 ring formation with the help of the FliO scaffold, followed by FliQ, FliR, and FlhB and finally FlhA during MS ring formation.

  19. Biosynthesis of Dictyostelium Discoideum Differentation-Inducing Factor by a Hybrid Type I Fatty Acid A-Type III polyketide synthase

    Energy Technology Data Exchange (ETDEWEB)

    Austin,M.; Saito, T.; Bowman, M.; Haydock, S.; Kato, A.; Moore, B.; Kay, R.; Noel, J.

    2006-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two {approx}3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis.

  20. Purification, crystal structure determination and functional characterization of type III antifreeze proteins from the European eelpout Zoarces viviparus

    DEFF Research Database (Denmark)

    Wilkens, Casper; Poulsen, Jens-Christian Navarro; Ramløv, Hans;

    2014-01-01

    Antifreeze proteins (AFPs) are essential components of many organisms adaptation to cold temperatures. Fish type III AFPs are divided into two groups, SP isoforms being much less active than QAE1 isoforms. Two type III AFPs from Zoarces viviparus, a QAE1 (ZvAFP13) and an SP (ZvAFP6) isoform...

  1. Type III secretion system genes of Dickeya dadantii 3937 are induced by plant phenolic acids.

    Directory of Open Access Journals (Sweden)

    Shihui Yang

    Full Text Available BACKGROUND: Dickeya dadantii is a broad-host range phytopathogen. D. dadantii 3937 (Ech3937 possesses a type III secretion system (T3SS, a major virulence factor secretion system in many gram-negative pathogens of plants and animals. In Ech3937, the T3SS is regulated by two major regulatory pathways, HrpX/HrpY-HrpS-HrpL and GacS/GacA-rsmB-RsmA pathways. Although the plant apoplast environment, low pH, low temperature, and absence of complex nitrogen sources in media have been associated with the induction of T3SS genes of phytobacteria, no specific inducer has yet been identified. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we identified two novel plant phenolic compounds, o-coumaric acid (OCA and t-cinnamic acid (TCA, that induced the expression of T3SS genes dspE (a T3SS effector, hrpA (a structural protein of the T3SS pilus, and hrpN (a T3SS harpin in vitro. Assays by qRT-PCR showed higher amounts of mRNA of hrpL (a T3SS alternative sigma factor and rsmB (an untranslated regulatory RNA, but not hrpS (a sigma(54-enhancer binding protein of Ech3937 when these two plant compounds were supplemented into minimal medium (MM. However, promoter activity assays using flow cytometry showed similar promoter activities of hrpN in rsmB mutant Ech148 grown in MM and MM supplemented with these phenolic compounds. Compared with MM alone, only slightly higher promoter activities of hrpL were observed in bacterial cells grown in MM supplemented with OCA/TCA. CONCLUSION/SIGNIFICANCE: The induction of T3SS expression by OCA and TCA is moderated through the rsmB-RsmA pathway. This is the first report of plant phenolic compounds that induce the expression T3SS genes of plant pathogenic bacteria.

  2. Evidence for alternative quaternary structure in a bacterial Type III secretion system chaperone

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Zhang, Lingling; Picking, Wendy L.; Geisbrecht, Brian V. (UMKC); (OKLU)

    2010-10-05

    Type III secretion systems are a common virulence mechanism in many Gram-negative bacterial pathogens. These systems use a nanomachine resembling a molecular needle and syringe to provide an energized conduit for the translocation of effector proteins from the bacterial cytoplasm to the host cell cytoplasm for the benefit of the pathogen. Prior to translocation specialized chaperones maintain proper effector protein conformation. The class II chaperone, Invasion plasmid gene (Ipg) C, stabilizes two pore forming translocator proteins. IpgC exists as a functional dimer to facilitate the mutually exclusive binding of both translocators. In this study, we present the 3.3 {angstrom} crystal structure of an amino-terminally truncated form (residues 10-155, denoted IpgC10-155) of the class II chaperone IpgC from Shigella flexneri. Our structure demonstrates an alternative quaternary arrangement to that previously described for a carboxy-terminally truncated variant of IpgC (IpgC{sup 1-151}). Specifically, we observe a rotationally-symmetric 'head-to-head' dimerization interface that is far more similar to that previously described for SycD from Yersinia enterocolitica than to IpgC1-151. The IpgC structure presented here displays major differences in the amino terminal region, where extended coil-like structures are seen, as opposed to the short, ordered alpha helices and asymmetric dimerization interface seen within IpgC{sup 1-151}. Despite these differences, however, both modes of dimerization support chaperone activity, as judged by a copurification assay with a recombinant form of the translocator protein, IpaB. Conclusions: From primary to quaternary structure, these results presented here suggest that a symmetric dimerization interface is conserved across bacterial class II chaperones. In light of previous data which have described the structure and function of asymmetric dimerization, our results raise the possibility that class II chaperones may

  3. Inheritance of Pantoea type III secretion systems through both vertical and horizontal transfer.

    Science.gov (United States)

    Kirzinger, Morgan W B; Butz, Cory J; Stavrinides, John

    2015-12-01

    The type III secretion system (T3SS) is an extracellular apparatus used by many Gram-negative bacteria to deliver effector proteins directly into plant and animal cells, thereby facilitating host-specific association. Strains of the enterobacterial genus, Pantoea, have been isolated from a wide variety of hosts, including plants, insects, and humans, yet it is unclear whether the T3SS may be involved in these associations. In this study, we use comparative genomics and phylogenetic methods to examine the origin and distribution of T3SSs in 35 sequenced environmental and clinical strains of Pantoea. We began our analysis by examining the distribution of the previously characterized plant cell-specific PSI-1 and animal cell-specific PSI-2 of the plant pathogenic Pantoea stewartii subsp. stewartii DC283 (PstDC283), and showed that both had a somewhat limited distribution. Our analysis, however, identified two variants of a unique plant cell-specific T3SS (PSI-1a and PSI-1b) in six Pantoea strains, including a clinical isolate. Our genome analysis of PstDC283 also identified a third T3SS that we named PSI-3, which has a similar genetic content and organization to the Salmonella, animal cell-specific SPI-2 system. Phylogenetic analysis of all three systems suggests that the PSI-1 system has been inherited vertically, whereas the newly identified PSI-1a and PSI-1b systems have been acquired independently from other genera within the Enterobacteriaceae. PSI-2 appears to have been acquired horizontally as far back as the Erwinia/Pantoea common ancestor, with evidence of more recent horizontal acquisition of the PSI-3 system. Our results suggest that Pantoea is a relatively old plant pathogen that has lost and subsequently regained different plant-associated T3SSs. This work has broad implications for understanding the host-associating capacity of Pantoea strains, and reveals the propensity for Pantoea isolates to exchange pathogenicity determinants with human

  4. Evidence for alternative quaternary structure in a bacterial Type III secretion system chaperone

    Directory of Open Access Journals (Sweden)

    Picking Wendy L

    2010-07-01

    Full Text Available Abstract Background Type III secretion systems are a common virulence mechanism in many Gram-negative bacterial pathogens. These systems use a nanomachine resembling a molecular needle and syringe to provide an energized conduit for the translocation of effector proteins from the bacterial cytoplasm to the host cell cytoplasm for the benefit of the pathogen. Prior to translocation specialized chaperones maintain proper effector protein conformation. The class II chaperone, Invasion plasmid gene (Ipg C, stabilizes two pore forming translocator proteins. IpgC exists as a functional dimer to facilitate the mutually exclusive binding of both translocators. Results In this study, we present the 3.3 Å crystal structure of an amino-terminally truncated form (residues 10-155, denoted IpgC10-155 of the class II chaperone IpgC from Shigella flexneri. Our structure demonstrates an alternative quaternary arrangement to that previously described for a carboxy-terminally truncated variant of IpgC (IpgC1-151. Specifically, we observe a rotationally-symmetric "head-to- head" dimerization interface that is far more similar to that previously described for SycD from Yersinia enterocolitica than to IpgC1-151. The IpgC structure presented here displays major differences in the amino terminal region, where extended coil-like structures are seen, as opposed to the short, ordered alpha helices and asymmetric dimerization interface seen within IpgC1-151. Despite these differences, however, both modes of dimerization support chaperone activity, as judged by a copurification assay with a recombinant form of the translocator protein, IpaB. Conclusions From primary to quaternary structure, these results presented here suggest that a symmetric dimerization interface is conserved across bacterial class II chaperones. In light of previous data which have described the structure and function of asymmetric dimerization, our results raise the possibility that class II

  5. Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins.

    Directory of Open Access Journals (Sweden)

    Lin Jin

    2016-05-01

    Full Text Available Bacterial AvrE-family Type-III effector proteins (T3Es contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A heterotrimeric enzyme complexes via direct interaction with B' regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000, associates with specific PP2A B' subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B' subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B' subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B' subunits was observed. These results indicate that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family.

  6. Ethylene polymerization by PN3-type pincer chromium(III) complexes

    KAUST Repository

    Gong, Dirong

    2014-12-01

    Chromium (III) complexes, Cr1, [2,6-(tBu2PNH) 2C5H4N]CrCl3; Cr2, [2,6-(Ph 2PNH)2C5H4N]CrCl3; Cr3, [2-(tBu2PNH)C5H4N]CrCl3 THF; Cr4, [6-(tBu2PNH)C5H4N-2- CH2NEt2]CrCl3; Cr5, [6-(tBu 2PNH)C5H4N-2-C3H2N 2]CrCl3; Cr6, [6-(tBu2PNH)C 5H4N-2-(3,5-Me2)C3H 2N2]CrCl3; Cr7, [6-(tBu 2PNH)C5H4N-2-(3,5-iPr 2)C3H2N2]CrCl3; Cr8, [6-(tBu2PNH)C5H4N-2-(3,5-Ph 2)C3H2N2]CrCl3, bearing a family of neutral PN3-type pincer ligands have been prepared. The molecular structure of Cr2 was further elucidated by the X-ray crystallographic analysis, showing an octahedral geometry. Treatment of these complexes with MAO or alkylaluminum led to catalysts with moderate activities (about 105 g (PE)/Cr(mol) h) for ethylene polymerization, affording exclusively linear low molecular weight solid PE without any detectable oligomers. Among Cr1-Cr8, the highest activity was achieved for Cr1/MAO at room temperature with production of PE with highest molecular weight, indicating that replacement of both tBu groups in Cr1 with Ph groups, or one PtBu2 with the N (imine) arm, resulted in a lower catalytic activity and lower M w. © 2014 Elsevier B.V.

  7. Expression of transforming growth factor-beta receptors types II and III within various cells in the rat periodontium.

    Science.gov (United States)

    Gao, J; Symons, A L; Bartold, P M

    1999-02-01

    This study reports the immunohistochemical localization of TGF-beta receptor type II (T beta R-II) and type III (T beta R-III) in cells of the forming periodontal ligament (PDL) in rat first molar roots. Mandibular periodontium was obtained from 3, 6 and 12-wk-old rats. This represented tissue from the initial, pre-mature and post-mature stages of root and periodontal development, respectively. Mandibular bone chips and molar roots were used to isolate osteoblasts, fibroblasts and cementoblasts. Cells were obtained using a 2-step trypsinization and explant technique, and cultured in Dulbecco's modification of Eagle's medium (DMEM) under routine cell culture conditions. Cells were cultured on coverslips for the purpose of detecting TGF-beta receptors, and compared with whole tissue sections using the same detection method. Cells which stained positively for T beta R-II and T beta R-III on both paraffin sections and cultured cell slides were counted. Both receptors were expressed in the various periodontal tissue compartments. PDL fibroblasts, cementoblasts and osteoblasts were stained positively for T beta R-II and T beta R-III. Endothelial cells were noted to be positive for T beta R-II only. T beta R-II was more widely distributed in cells than T beta R-III, but T beta R-III was extensively localized in the extracellular matrix. Both receptors were expressed on the cell membrane and also localized in the cytoplasm. The findings for paraffin sections were consistent with the immunohistochemical staining of cultured cells. The percentage of cells which stained positively for T beta R-II was greater (approximately 85%) than that for T beta R-III (approximately 60%) in all major types of the PDL cells on both paraffin sections and cultured cell slides. Extensive location of TGF-beta receptors in both cells and extracellular matrix suggests that several binding sites are available for TGF-beta s to interact with target cells during development and following maturation

  8. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized

  9. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia

  10. Characteristics of type III bursts in the solar wind from simultaneous observations on board ISEE-3 and Voyager

    Science.gov (United States)

    Lecacheux, A.; Steinberg, J.-L.; Hoang, S.; Dulk, G. A.

    1989-01-01

    The properties of solar type III bursts observed aboard ISEE-3 and Voyager that originate behind the sun are analyzed and compared to those originating on the near side. The measurement of the burst parameters and the correction for proximity effects are described. The diminution of flux densities, the increase of source sizes, the difference of source azimuths and elevations, the change of spectral properties, and the anomalous delays in burst arrival time at one spacecraft relative to another are determined. Many of the observations imply that the beaming of type III radiation is much more widespread at all frequencies than has been derived from statistical studies. The effective beam appears to consist of at least two components: a Gaussian core of half width about 60 deg, and a very broad halo that extends to 180 deg with an amplitude of a few percent.

  11. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via their acti......During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...... their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo-epitopes may be used as markers of fibrosis....

  12. Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients

    Science.gov (United States)

    Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

    2017-01-01

    Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials. PMID:28122039

  13. Structure of the cytoplasmic domain of Yersinia pestis YscD, an essential component of the type III secretion system

    Energy Technology Data Exchange (ETDEWEB)

    Lountos, George T.; Tropea, Joseph E.; Waugh, David S. (SAIC); (NCI)

    2012-09-17

    The Yersinia pestis YscD protein is an essential component of the type III secretion system. YscD consists of an N-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). Both the cytoplasmic and the periplasmic domains are required for the assembly of the type III secretion system. Here, the structure of the YscD cytoplasmic domain solved by SAD phasing is presented. Although the three-dimensional structure is similar to those of forkhead-associated (FHA) domains, comparison with the structures of canonical FHA domains revealed that the cytoplasmic domain of YscD lacks the conserved residues that are required for binding phosphothreonine and is therefore unlikely to function as a true FHA domain.

  14. Crystallization and preliminary crystallographic analysis of an acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Hiroyuki [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan); Kondo, Shin; Kato, Ryohei [Innovation Center Yokohama, Mitsubishi Chemical Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Wanibuchi, Kiyofumi; Noguchi, Hiroshi [School of Pharmaceutical Sciences, University of Shizuoka and the COE21 Program, Shizuoka 422-8526 (Japan); Sugio, Shigetoshi, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [Innovation Center Yokohama, Mitsubishi Chemical Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Ikuro, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [School of Pharmaceutical Sciences, University of Shizuoka and the COE21 Program, Shizuoka 422-8526 (Japan); PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kohno, Toshiyuki, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan)

    2007-07-01

    An acridone-producing novel type III polyketide synthase from H. serrata has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.0 Å. Polyketide synthase 1 (PKS1) from Huperzia serrata is a plant-specific type III polyketide synthase that shows an unusually versatile catalytic potential, producing various aromatic tetraketides, including chalcones, benzophenones, phlorogulucinols and acridones. Recombinant H. serrata PKS1 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to space group I222 or I2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 73.3, b = 85.0, c = 137.7 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.0 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  15. Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients.

    Science.gov (United States)

    Chen, Xing; Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

    2017-01-01

    Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials.

  16. Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis

    DEFF Research Database (Denmark)

    Richardot, P; Charni-Ben Tabassi, N; Toh, L

    2009-01-01

    OBJECTIVES: Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA. METHODS...... in healthy controls and significantly correlated with C-reactive protein values (r=0.40, Pcollagen N-telopeptide is increased in the synovial tissue of patients with knee OA. Measurements of serum IIINys level may be useful for the clinical......: A polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n=4) and rheumatoid arthritis (RA, n=4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme...

  17. STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : III. AN IMPROVED METHOD FOR THE ISOLATION OF THE TRANSFORMING SUBSTANCE AND ITS APPLICATION TO PNEUMOCOCCUS TYPES II, III, AND VI.

    Science.gov (United States)

    McCarty, M; Avery, O T

    1946-01-31

    1. An improved method is outlined for the isolation and purification of the pneumococcal transforming substance. This method makes use of the fact that citrate inhibits the destructive action of the enzyme, desoxyribonuclease, which is released together with the active material during lysis of the living bacterial cells. A fivefold greater yield of purified transforming agent is obtained by the present method than by the procedure previousiy described. 2. The specific transforming substance has been isolated from pneumococci of types II and VI, in addition to Type III. In each instance the biologically active material has been found to consist of desoxyribonucleic acid.

  18. Comparison of backbone dynamics of the type III antifreeze protein and antifreeze-like domain of human sialic acid synthase

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yong-Geun [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of); Park, Chin-Ju [Gwangju Institute of Science and Technology, Division of Liberal Arts and Sciences and Department of Chemistry (Korea, Republic of); Kim, Hee-Eun; Seo, Yeo-Jin; Lee, Ae-Ree; Choi, Seo-Ree; Lee, Shim Sung; Lee, Joon-Hwa, E-mail: joonhwa@gnu.ac.kr [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of)

    2015-02-15

    Antifreeze proteins (AFPs) are found in a variety of cold-adapted (psychrophilic) organisms to promote survival at subzero temperatures by binding to ice crystals and decreasing the freezing temperature of body fluids. The type III AFPs are small globular proteins that consist of one α-helix, three 3{sub 10}-helices, and two β-strands. Sialic acids play important roles in a variety of biological functions, such as development, recognition, and cell adhesion and are synthesized by conserved enzymatic pathways that include sialic acid synthase (SAS). SAS consists of an N-terminal catalytic domain and a C-terminal antifreeze-like (AFL) domain, which is similar to the type III AFPs. Despite having very similar structures, AFL and the type III AFPs exhibit very different temperature-dependent stability and activity. In this study, we have performed backbone dynamics analyses of a type III AFP (HPLC12 isoform) and the AFL domain of human SAS (hAFL) at various temperatures. We also characterized the structural/dynamic properties of the ice-binding surfaces by analyzing the temperature gradient of the amide proton chemical shift and its correlation with chemical shift deviation from random coil. The dynamic properties of the two proteins were very different from each other. While HPLC12 was mostly rigid with a few residues exhibiting slow motions, hAFL showed fast internal motions at low temperature. Our results provide insight into the molecular basis of thermostability and structural flexibility in homologous psychrophilic HPLC12 and mesophilic hAFL proteins.

  19. Determination of the Stoichiometry of the Complete Bacterial Type III Secretion Needle Complex Using a Combined Quantitative Proteomic Approach*

    Science.gov (United States)

    Zilkenat, Susann; Franz-Wachtel, Mirita; Stierhof, York-Dieter; Galán, Jorge E.; Macek, Boris; Wagner, Samuel

    2016-01-01

    Precisely knowing the stoichiometry of their components is critical for investigating structure, assembly, and function of macromolecular machines. This has remained a technical challenge in particular for large, hydrophobic membrane-spanning protein complexes. Here, we determined the stoichiometry of a type III secretion system of Salmonella enterica serovar Typhimurium using two complementary protocols of gentle complex purification combined with peptide concatenated standard and synthetic stable isotope-labeled peptide-based mass spectrometry. Bacterial type III secretion systems are cell envelope-spanning effector protein-delivery machines essential for colonization and survival of many Gram-negative pathogens and symbionts. The membrane-embedded core unit of these secretion systems, termed the needle complex, is composed of a base that anchors the machinery to the inner and outer membranes, a hollow filament formed by inner rod and needle subunits that serves as conduit for substrate proteins, and a membrane-embedded export apparatus facilitating substrate translocation. Structural analyses have revealed the stoichiometry of the components of the base, but the stoichiometry of the essential hydrophobic export apparatus components and of the inner rod protein remain unknown. Here, we provide evidence that the export apparatus of type III secretion systems contains five SpaP, one SpaQ, one SpaR, and one SpaS. We confirmed that the previously suggested stoichiometry of nine InvA is valid for assembled needle complexes and describe a loose association of InvA with other needle complex components that may reflect its function. Furthermore, we present evidence that not more than six PrgJ form the inner rod of the needle complex. Providing this structural information will facilitate efforts to obtain an atomic view of type III secretion systems and foster our understanding of the function of these and related flagellar machines. Given that other virulence

  20. The Dynamics of an Impulsive Predator-Prey System with Stage Structure and Holling Type III Functional Response

    Directory of Open Access Journals (Sweden)

    Zhixiang Ju

    2015-01-01

    Full Text Available Based on the biological resource management of natural resources, a stage-structured predator-prey model with Holling type III functional response, birth pulse, and impulsive harvesting at different moments is proposed in this paper. By applying comparison theorem and some analysis techniques, the global attractivity of predator-extinction periodic solution and the permanence of this system are studied. At last, examples and numerical simulations are given to verify the validity of the main results.

  1. Type III Effector Diversification via Both Pathoadaptation and Horizontal Transfer in Response to a Coevolutionary Arms Race

    OpenAIRE

    Wenbo Ma; Dong, Frederick F. T; John Stavrinides; David S. Guttman

    2006-01-01

    The concept of the coevolutionary arms race holds a central position in our understanding of pathogen-host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae an...

  2. Determination of the Stoichiometry of the Complete Bacterial Type III Secretion Needle Complex Using a Combined Quantitative Proteomic Approach.

    Science.gov (United States)

    Zilkenat, Susann; Franz-Wachtel, Mirita; Stierhof, York-Dieter; Galán, Jorge E; Macek, Boris; Wagner, Samuel

    2016-05-01

    Precisely knowing the stoichiometry of their components is critical for investigating structure, assembly, and function of macromolecular machines. This has remained a technical challenge in particular for large, hydrophobic membrane-spanning protein complexes. Here, we determined the stoichiometry of a type III secretion system of Salmonella enterica serovar Typhimurium using two complementary protocols of gentle complex purification combined with peptide concatenated standard and synthetic stable isotope-labeled peptide-based mass spectrometry. Bacterial type III secretion systems are cell envelope-spanning effector protein-delivery machines essential for colonization and survival of many Gram-negative pathogens and symbionts. The membrane-embedded core unit of these secretion systems, termed the needle complex, is composed of a base that anchors the machinery to the inner and outer membranes, a hollow filament formed by inner rod and needle subunits that serves as conduit for substrate proteins, and a membrane-embedded export apparatus facilitating substrate translocation. Structural analyses have revealed the stoichiometry of the components of the base, but the stoichiometry of the essential hydrophobic export apparatus components and of the inner rod protein remain unknown. Here, we provide evidence that the export apparatus of type III secretion systems contains five SpaP, one SpaQ, one SpaR, and one SpaS. We confirmed that the previously suggested stoichiometry of nine InvA is valid for assembled needle complexes and describe a loose association of InvA with other needle complex components that may reflect its function. Furthermore, we present evidence that not more than six PrgJ form the inner rod of the needle complex. Providing this structural information will facilitate efforts to obtain an atomic view of type III secretion systems and foster our understanding of the function of these and related flagellar machines. Given that other virulence

  3. [Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years].

    Science.gov (United States)

    Kalinke, D U; Wüthrich, B

    1999-01-01

    A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.

  4. Minifilament Eruption as the Source of a Blowout Jet, C-class Flare, and Type-III Radio Burst

    Science.gov (United States)

    Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Li, Haidong; Xu, Zhe

    2017-01-01

    We report a strong minifilament eruption associated with Geostationary Operational Environmental Satellite C1.6 flare and WIND type-III radio burst. The minifilament, which lies at the periphery of active region 12259, is detected by Hα images from the New Vacuum Solar Telescope. The minifilament undergoes a partial and then a full eruption. Simultaneously, two co-spatial jets are successively observed in extreme ultraviolet images from the Solar Dynamic Observatory. The first jet exhibits a typical fan-spine geometry, suggesting that the co-spatial minifilament is possibly embedded in magnetic fields with a fan-spine structure. However, the second jet displays blowout morphology when the entire minifilament erupts upward, leaving behind a hard X-ray emission source in the base. Differential emission measure analyses show that the eruptive region is heated up to about 4 MK during the fan-spine jet, while up to about 7 MK during the blowout jet. In particular, the blowout jet is accompanied by an interplanetary type-III radio burst observed by WIND/WAVES in the frequency range from above 10 to 0.1 MHz. Hence, the minifilament eruption is correlated with the interplanetary type-III radio burst for the first time. These results not only suggest that coronal jets can result from magnetic reconnection initiated by erupting minifilaments with open fields, but also shed light on the potential influence of minifilament eruption on interplanetary space.

  5. On the Brightness and Waiting-time Distributions of a Type III Radio Storm observed by STEREO/WAVES

    CERN Document Server

    Eastwood, J P; Hudson, H S; Krucker, S; Bale, S D; Maksimovic, M; Goetz, K; Bougeret, J -L

    2009-01-01

    Type III solar radio storms, observed at frequencies below approximately 16 MHz by space borne radio experiments, correspond to the quasi-continuous, bursty emission of electron beams onto open field lines above active regions. The mechanisms by which a storm can persist in some cases for more than a solar rotation whilst exhibiting considerable radio activity are poorly understood. To address this issue, the statistical properties of a type III storm observed by the STEREO/WAVES radio experiment are presented, examining both the brightness distribution and (for the first time) the waiting-time distribution. Single power law behavior is observed in the number distribution as a function of brightness; the power law index is approximately 2.1 and is largely independent of frequency. The waiting-time distribution is found to be consistent with a piecewise-constant Poisson process. This indicates that during the storm individual type III bursts occur independently and suggests that the storm dynamics are consiste...

  6. Diagnose Physical Conditions Near the Flare Energy-release Sites from Observations of Solar Microwave Type III Bursts

    CERN Document Server

    Tan, Baolin; Meszarosova, Hana; Huang, Guangli

    2015-01-01

    In the physics of solar flares, it is crucial to diagnose the physical conditions near the flare energy-release sites. However, so far it is unclear how do diagnose these physical conditions. Solar microwave type III burst is believed to be a sensitive signature of the primary energy release and electron accelerations in solar flares. This work takes into account the effect of magnetic field on the plasma density and developed s set of formulas which can be used to estimate the plasma density, temperature, magnetic field near the magnetic reconnection site and particle acceleration region, and the velocity and energy of electron beams. We applied these formulas to three groups of microwave type III pairs in a X-class flare, and obtained some reasonable and interesting results. This method can be applied to other microwave type III bursts to diagnose the physical conditions of source regions, and provide some basic information to understand the intrinsic nature and fundamental processes occurring near the flar...

  7. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Microwave Type III Pairs

    CERN Document Server

    Tan, Baolin; Meszarosova, Hana; Kashapova, Larisa; Huang, Jing; Yan, Yan; Kontar, Eduard P

    2016-01-01

    This work reports a peculiar and interesting train of microwave type III pair bursts in the impulsive rising phase of a solar flare on 2011 September 26. The observations include radio spectrometers at frequency of 0.80 - 2.00 GHz, hard X-ray (RHESSI and FERMI), EUV images of SWAP/PROBA-2 and magnetogram of HMI/SDO. By using a recently developed method (Tan et al. 2016a), we diagnosed the plasma density, temperature, plasma beta, magnetic field near the source region, the energy of energetic electrons and the distance between the acceleration region and the emission start sites of type III bursts. From the diagnostics, we find that: (1) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites almost have no obvious variations during the period of type III pair trains, while the energy of electrons has an obvious peak value which is consistent to the hard X-ray emission. (2) The plasma beta is much higher than an unity showing a highly dynam...

  8. Chlamydia pneumoniae CopD translocator protein plays a critical role in type III secretion (T3S and infection.

    Directory of Open Access Journals (Sweden)

    David C Bulir

    Full Text Available Pathogenic Gram-negative bacteria use type III secretion (T3S to inject effector proteins into the host cell to create appropriate conditions for infection and intracellular replication. Chlamydia spp. are believed to use T3S to infect their host cell, and the translocator proteins are an essential component of this system. Chlamydia pneumoniae contains genes encoding two sets of translocator proteins; CopB and CopD, and CopB2 and CopD2. In this study, we identified novel interactions between CopD and three type III secretion proteins; namely, CopN, CdsN, and CdsF. We identified a CopD putative chaperone binding motif, PxLxxP, within the N-terminal region (CopD amino acids 120-125, which was necessary for interaction with its putative chaperone LcrH_1. Using size exclusion chromatography, we showed that CopD and LcrH_1 formed higher order structures in solution with CopD and LcrH_1 binding in a ratio of 1∶1, which is unique for T3SS translocator proteins. Lastly, we showed that antibodies to CopD reduced C. pneumoniae infectivity by >95%. Collectively, this data suggests that CopD plays a critical role in pathogenesis and likely functions as a hydrophobic translocator of the type III secretion system in Chlamydia pneumoniae.

  9. Phase Coupling in Langmuir Wave Packets: Evidence for Four Wave Interactions in Solar Type III Radio Bursts

    Science.gov (United States)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    The four wave interaction process, known as the oscillating two stream instability (OTSI) is considered as one of the mechanisms responsible for stabilizing the electron beams associated with solar type III radio bursts. It has been reported that (1) an intense localized Langmuir wave packet associated with a type III burst contains the spectral characteristics of the OTSI: (a) a resonant peak at the local electron plasma frequency, f(sub pe), (b) a Stokes peak at a frequency slightly lower than f(sub pe), (c) anti-Stokes peak at a frequency slightly higher than f(sub pe), and (d) a low frequency enhancement below a few hundred Hz, (2) the frequencies and wave numbers of these spectral components satisfy the resonance conditions of the OTSI, and (3) the peak intensity of the wave packet is well above the thresholds for the OTSI as well as spatial collapse of envelope solitons. Here, for the first time, applying the trispectral analysis on this wave packet, we show that the tricoherence, which measures the degree of coherent four-wave coupling amongst the observed spectral components exhibits a peak. This provides an additional evidence for the OTSI and related spatial collapse of Langmuir envelope solitons in type III burst sources.

  10. [Clavicular hook plate combined with suture anchor for the treatment of type Tossy III chronic acromioclavicular dislocation].

    Science.gov (United States)

    Xu, Zhi-Bin; Wang, Jin

    2014-05-01

    To observe the clinical effects of clavicular hook plate combined with suture anchor in treating type Tossy III chronic acromioclavicular dislocation. From January 2008 to December 2012,18 patients with type Tossy III chronic acromioclavicular dislocation were treated with clavicular hook plate and suture anchor. There were 12 males and 6 females, aged from 20 to 56 years old with an average of 31.5 years. Ten cases were left dislocation and 8 cases were right dislocation. Operation time was 3 weeks to 4 months after injury with a mean of 1.8 months. Functional exercise was adopted 2 weeks after operation. And Karlsson standard was used to evaluate curative effect. All patients were followed up for 6 to 24 months with an average of 16 months. According to Karlsson standard, 17 cases were excellent and 1 was poor. Clavicular hook plate combined with suture anchor can repair conoid ligament and trapezoid ligament in treating type Tossy III chronic acromioclavicular dislocation, and had advantages of simple operation, less trauma, stable fixation, it can obtain satisfactory effects.

  11. T346Hunter: a novel web-based tool for the prediction of type III, type IV and type VI secretion systems in bacterial genomes.

    Directory of Open Access Journals (Sweden)

    Pedro Manuel Martínez-García

    Full Text Available T346Hunter (Type Three, Four and Six secretion system Hunter is a web-based tool for the identification and localisation of type III, type IV and type VI secretion systems (T3SS, T4SS and T6SS, respectively clusters in bacterial genomes. Non-flagellar T3SS (NF-T3SS and T6SS are complex molecular machines that deliver effector proteins from bacterial cells into the environment or into other eukaryotic or prokaryotic cells, with significant implications for pathogenesis of the strains encoding them. Meanwhile, T4SS is a more functionally diverse system, which is involved in not only effector translocation but also conjugation and DNA uptake/release. Development of control strategies against bacterial-mediated diseases requires genomic identification of the virulence arsenal of pathogenic bacteria, with T3SS, T4SS and T6SS being major determinants in this regard. Therefore, computational methods for systematic identification of these specialised machines are of particular interest. With the aim of facilitating this task, T346Hunter provides a user-friendly web-based tool for the prediction of T3SS, T4SS and T6SS clusters in newly sequenced bacterial genomes. After inspection of the available scientific literature, we constructed a database of hidden Markov model (HMM protein profiles and sequences representing the various components of T3SS, T4SS and T6SS. T346Hunter performs searches of such a database against user-supplied bacterial sequences and localises enriched regions in any of these three types of secretion systems. Moreover, through the T346Hunter server, users can visualise the predicted clusters obtained for approximately 1700 bacterial chromosomes and plasmids. T346Hunter offers great help to researchers in advancing their understanding of the biological mechanisms in which these sophisticated molecular machines are involved. T346Hunter is freely available at http://bacterial-virulence-factors.cbgp.upm.es/T346Hunter.

  12. Titanocene(III)-promoted Barbier-type crotylation of carbonyl compounds.

    Science.gov (United States)

    Sancho-Sanz, Iris; Miguel, Delia; Millán, Alba; Estévez, Rosa E; Oller-López, Juan L; Álvarez-Manzaneda, Enrique; Robles, Rafael; Cuerva, Juan M; Justicia, José

    2011-01-21

    A mild, highly regio- and stereoselective method for the crotylation of aldehydes and ketones mediated/catalyzed by titanocene(III) is described. Optimized conditions permit the selective generation of γ-adducts in high yields together with high stereoselectivity, with a predominance of anti stereoisomers.

  13. High frequency of multidrug-resistant Staphylococcus aureus with SCCmec type III and Spa types t037 and t631 isolated from burn patients in southwest of Iran.

    Science.gov (United States)

    Parhizgari, Najmeh; Khoramrooz, Seyed Sajjad; Malek Hosseini, Seyed Ali Asghar; Marashifard, Masoud; Yazdanpanah, Mahboobeh; Emaneini, Mohammad; Gharibpour, Farzaneh; Mirzaii, Mehdi; Darban-Sarokhalil, Davood; Moein, Masoud; Naraki, Mahmood

    2016-03-01

    Methicilin resistance Staphylococcus aureus (MRSA) infections are the major challenges in hospitals, especially in the burn units. The use of molecular typing methods is essential for tracking the spread of S. aureus infection and epidemiological investigations. The aim of this study was to find the profile of the spa types and also the prevalence of each SCCmec type of S. aureus strains in a central burn hospital in southwest of Iran. A total of 81 non-duplicate S. aureus were isolated from burn patients between April 2011 and February 2012. The susceptibility of the isolates against 13 different antibiotics was tested by disk agar diffusion (DAD) method. MRSA strains were identified by amplification of mecA gene. Multiplex-polymerase chain reaction (PCR) technique was used to determine the SCCmec types of MRSA strains and all the S. aureus isolates were typed by spa typing method. Detection of mecA gene showed that 70 (86.4%) of the isolates were MRSA. The highest rate of resistance was observed for penicillin (97.5%) and erythromycin (77.8%). None of the isolates were resistant to vancomycin. Sixty-seven of the 70 MRSA isolates harbored only SCCmec type III and three untypeable isolates. Five different spa types were detected. The most common spa types were t037 (42.5%) and t631 (34.5%) and were only found in MRSA isolates. Only SCCmec type III was found in burn patients which emphasizes the HA-MRSA origin of these strains. Only five different spa types identified in this study are in accordance with one SCCmec type which indicates that a limited number of bacterial colons are circulated in the burn unit in this hospital.

  14. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

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    Shigeto Yoshida

    2007-12-01

    Full Text Available The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50 of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions.

  15. Endoscopic treatment of choledochal cyst type III Tratamento endoscópico de cisto de colédoco do tipo III

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    Matheus Alessi Rodrigues

    2008-09-01

    Full Text Available BACKGROUND: Todani type III cysts are not very common disease. Endoscopically the choledochocele is not a challenging diagnosis. Sometimes biliary stone disease is associated and events of cholangitis and pancreatitis may occur. Normally these patients are referred for surgical treatment, mainly because there is a widespread concept that choledocal cysts are very prone to develop neoplasia and must be resected. Nevertheless surgical resection is not free of morbidity. The chance for neoplasia in such cases seems to be related to the presence of pancreaticobiliary reflux towards the common bile duct. AIM: To report a case of endoscopic treatment of choledochal cyst type III with literature review. CASE REPORT: Young man with recurrent abdominal pain, fever and hyperamylasemia. An ERCP showed pancreaticobiliary maljunction and calculus impaction. Papillotomy was performed and complete biliary clearance was achieved. Amylase contents in the common bile duct was measured and normal. Due to absence of pancreatiobiliary reflux, a second endoscopic approach was performed and a wide communication between choledochocele and duodenum was done with diathermy (using the papillotome. The patient recovering was uneventful and in 30 months follow-up he remains asymptomatic. CONCLUSION: Since pancreatobiliary reflux is not present, surgical approach of the diverticulum seemed to be not necessary. Endoscopic drainage of choledococele was a good option for conservative treatment.INTRODUÇÃO: Cisto de colédoco do tipo III de Todani não é doença muito comum. Eventualmente pode ocorrer a presença de doença biliar calculosa, que nestes casos estaria associada a eventos de colangite e pancreatite. Normalmente estes pacientes são conduzidos ao tratamento cirúrgico, principalmente porque há conceito difundido de que os cistos de colédoco são muito propensos a desenvolver neoplasia e que a sua presença indicaria ressecção cirúrgica. A chance para

  16. Progressive non-infectious anterior vertebral fusion in a baby with Saethre-Chotzen-acrocephalosyndactyly type III syndrome

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    Али Аль-Каисси

    2015-09-01

    Full Text Available We report on a 3-months old baby of Austrian origin and product of non-consanguineous parents. Abnormal craniofacial contour was the main deformity. The overall clinico-radiographic features were consistent with Saether-Chotzen-acrocephalosyndactyly type III syndrome. Bi-directional sequencing of the exon 8 and of the FGFR3-genes, exons 7 of FGFR3 (Fibroblast growth factor receptor3 genes, the exon 5 of the FGFR1 gene, revealed no mutations. Sagittal MRI imaging of the spine showed anterior vertebral fusion along the thoraco-lumbar vertebrae compatible with the non-infectious type.

  17. Two-Higgs-doublet type-II and -III models and t → ch at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Arhrib, A. [Universite Abdelmalek Essaadi, Departement de Mathematiques, Faculte des Sciences et Techniques, B. 416, Tangier (Morocco); National Center for Theoretical Sciences, Physics Division, Hsinchu (China); Benbrik, R. [Cadi Ayyad University, LPHEA, Semlalia, Marrakech (Morocco); Faculte Polydisciplinaire de Safi, MSISM Team, Sidi Bouzid, B.P 4162, Safi (Morocco); Chen, Chuan-Hung [National Cheng-Kung University, Department of Physics, Tainan (China); Gomez-Bock, Melina [Universidad de las Americas Puebla, DAFM, Cholula, PUE (Mexico); Semlali, Souad [Cadi Ayyad University, LPHEA, Semlalia, Marrakech (Morocco)

    2016-06-15

    We study the constraints of the generic two-Higgs-doublet model (2HDM) type-III and the impacts of the new Yukawa couplings. For comparisons, we revisit the analysis in the 2HDM type-II. To understand the influence of all involving free parameters and to realize their correlations, we employ a χ-square fitting approach by including theoretical and experimental constraints, such as the S, T, and U oblique parameters, the production of standard model Higgs and its decay to γγ, WW*/ZZ*, τ{sup +}τ{sup -}, etc. The errors of the analysis are taken at 68, 95.5, and 99.7% confidence levels. Due to the new Yukawa couplings being associated with cos(β - α) and sin(β - α), we find that the allowed regions for sin α and tan β in the type-III model can be broader when the dictated parameter χ{sub F} is positive; however, for negative χ{sub F}, the limits are stricter than those in the type-II model. By using the constrained parameters, we find that the deviation from the SM in h → Zγ can be of O(10 %). Additionally, we also study the top-quark flavor-changing processes induced at the tree level in the type-III model and find that when all current experimental data are considered, we get Br(t → c(h, H)) < 10{sup -3} for m{sub h} = 125.36 and m{sub h} = 150 GeV, and Br(t → cA) slightly exceeds 10{sup -3} for m{sub A} = 130 GeV. (orig.)

  18. Adjusting the log-Pearson type III function to even-aged eucalyptus stands data

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    Daniel Henrique Breda Binoti

    2014-12-01

    Full Text Available The objective of this study is to evaluate the efficiency of the log-Pearson tipo III function to describe the diameter structure of even-aged stands, and propose a diameter distribution model using the function. The modeling function performed by the log-Pearson tipo III was compared with the modeling performed with the Weibull function. For this we used data from permanent plots of eucalyptus, located in the Midwestern region of Minas Gerais. Adherence to the functions of the data was confirmed by applying the Kolmogorov-Smirnov test (KS. The diameter distribution models used were based on models proposed by Nogueira et al. (2005 and were evaluated in terms of RMSE (% and the correlation coefficient between estimated and observed values. All fitting to the data presented adherence by the KS test. All equations fitted for the recovery of the diameter distribution showed high correlation coefficients and can be used for modeling the diameter distribution of eucalyptus.

  19. IPS-1 is essential for type III IFN production by hepatocytes and dendritic cells in response to hepatitis C virus infection.

    Science.gov (United States)

    Okamoto, Masaaki; Oshiumi, Hiroyuki; Azuma, Masahiro; Kato, Nobuyuki; Matsumoto, Misako; Seya, Tsukasa

    2014-03-15

    Hepatitis C virus (HCV) is a major cause of liver disease. The innate immune system is essential for controlling HCV replication, and HCV is recognized by RIG-I and TLR3, which evoke innate immune responses through IPS-1 and TICAM-1 adaptor molecules, respectively. IL-28B is a type III IFN, and genetic polymorphisms upstream of its gene are strongly associated with the efficacy of polyethylene glycol-IFN and ribavirin therapy. As seen with type I IFNs, type III IFNs induce antiviral responses to HCV. Recent studies established the essential role of TLR3-TICAM-1 pathway in type III IFN production in response to HCV infection. Contrary to previous studies, we revealed an essential role of IPS-1 in type III IFN production in response to HCV. First, using IPS-1 knockout mice, we revealed that IPS-1 was essential for type III IFN production by mouse hepatocytes and CD8(+) dendritic cells (DCs) in response to cytoplasmic HCV RNA. Second, we demonstrated that type III IFN induced RIG-I but not TLR3 expression in CD8(+) DCs and augmented type III IFN production in response to cytoplasmic HCV RNA. Moreover, we showed that type III IFN induced cytoplasmic antiviral protein expression in DCs and hepatocytes but failed to promote DC-mediated NK cell activation or cross-priming. Our study indicated that IPS-1-dependent pathway plays a crucial role in type III IFN production by CD8(+) DCs and hepatocytes in response to HCV, leading to cytoplasmic antiviral protein expressions.

  20. [CrIII(NCMe)6]3+--a labile CrIII source enabling formation of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue-type magnetic materials.

    Science.gov (United States)

    Nelson, Kendric J; Daniels, Matthew C; Reiff, William M; Troff, Shayla A; Miller, Joel S

    2007-11-26

    The kinetic inertness of the hexaaquachromium(III) (kH2O=2.4x10(-6) s(-1)) has led to challenges with respect to incorporating CrIII ions into Prussian blue-type materials; however, hexakis(acetonitrile)chromium(III) was shown to be substantially more labile (approximately 10(4) times) and enables a new synthetic route for the synthesis of these materials via nonaqueous solvents. The synthesis, spectroscopic, and physical properties of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue analogues synthesized from [CrIII(NCMe)6]3+ and the corresponding [MIII(CN)6]3- are described. All these compounds {(NEt4)0.02CrIII[VIII(CN)6]0.98(BF4)(0.08).0.10MeCN (1), CrIII[CrIII(CN)6].0.16MeCN (2), CrIII[MnIII(CN)6].0.10MeCN (3), and (NEt4)0.04CrIII0.64CrIV0.40[FeII(CN)6]0.40[FeIII(CN)6]0.60(BF4)(0.16).1.02MeCN (4)} are ferrimagnets exhibiting cluster-glass behavior. Strong antiferromagnetic coupling was observed for M=V, Cr, and Mn with Weiss constants (theta) ranging from -132 to -524 K; and in 2, where the strongest coupling is observed (theta=-524 K), the highest Tc (110 K) value was observed. Weak antiferromagnetic coupling was observed for M=Fe (theta=-12 K) leading to the lowest Tc (3 K) value in this series. Weak coupling and the low Tc value observed in 4 were additionally contributed by the presence of both [FeII(CN)6]4- and [FeIII(CN)6]3- as confirmed by 57Fe-Mössbauer spectroscopy.

  1. Multiplex real-time PCR for detecting and typing Clostridium botulinum group III organisms and their mosaic variants.

    Science.gov (United States)

    Anniballi, Fabrizio; Auricchio, Bruna; Woudstra, Cédric; Fach, Patrick; Fiore, Alfonsina; Skarin, Hanna; Bano, Luca; Segerman, Bo; Knutsson, Rickard; De Medici, Dario

    2013-09-01

    Botulism is a neuroparalytic disease that can occur in all warm-blooded animals, birds, and fishes. The disease in animals is mainly caused by toxins produced by Clostridium botulinum strains belonging to group III, although outbreaks due to toxins produced by group I and II organisms have been recognized. Group III strains are capable of producing botulinum toxins of type C, D, and C/D and D/C mosaic variants. Definitive diagnosis of animal botulism is made by combining clinical findings with laboratory investigations. Detection of toxins in clinical specimens and feed is the gold standard for laboratory diagnosis. Since toxins may be degraded by organisms contained in the gastrointestinal tract or may be present at levels below the detection limit, the recovery of C. botulinum from sick animal specimens is consistent for laboratory confirmation. In this article we report the development and in-house validation of a new multiplex real-time PCR for detecting and typing the neurotoxin genes found in C. botulinum group III organisms. Validation procedures have been carried out according to ISO 16140, using strains and samples recovered from cases of animal botulism in Italy and France.

  2. Analysis of viral protein-2 encoding gene of avian encephalomyelitis virus from field specimens in Central Java region, Indonesia

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    Aris Haryanto

    2016-01-01

    Full Text Available Aim: Avian encephalomyelitis (AE is a viral disease which can infect various types of poultry, especially chicken. In Indonesia, the incidence of AE infection in chicken has been reported since 2009, the AE incidence tends to increase from year to year. The objective of this study was to analyze viral protein 2 (VP-2 encoding gene of AE virus (AEV from various species of birds in field specimen by reverse transcription polymerase chain reaction (RT-PCR amplification using specific nucleotides primer for confirmation of AE diagnosis. Materials and Methods: A total of 13 AEV samples are isolated from various species of poultry which are serologically diagnosed infected by AEV from some areas in central Java, Indonesia. Research stage consists of virus samples collection from field specimens, extraction of AEV RNA, amplification of VP-2 protein encoding gene by RT-PCR, separation of RT-PCR product by agarose gel electrophoresis, DNA sequencing and data analysis. Results: Amplification products of the VP-2 encoding gene of AEV by RT-PCR methods of various types of poultry from field specimens showed a positive results on sample code 499/4/12 which generated DNA fragment in the size of 619 bp. Sensitivity test of RT-PCR amplification showed that the minimum concentration of RNA template is 127.75 ng/μl. The multiple alignments of DNA sequencing product indicated that positive sample with code 499/4/12 has 92% nucleotide homology compared with AEV with accession number AV1775/07 and 85% nucleotide homology with accession number ZCHP2/0912695 from Genbank database. Analysis of VP-2 gene sequence showed that it found 46 nucleotides difference between isolate 499/4/12 compared with accession number AV1775/07 and 93 nucleotides different with accession number ZCHP2/0912695. Conclusions: Analyses of the VP-2 encoding gene of AEV with RT-PCR method from 13 samples from field specimen generated the DNA fragment in the size of 619 bp from one sample with

  3. Hawkins Group I fracture of neck of talus and Salter Harris Type III tibial epiphyseal injury of medial malleolus.

    Science.gov (United States)

    Prasad, Kodali Siva R K; Vali, Hamza; Hussain, Altaf

    2013-01-01

    We are reporting an unusual combination of Hawkins Group I fracture of the neck of left talus in association with Salter Harris Type III distal tibial epiphyseal injury of medial malleolus in a child with cerebral palsy and hemiplegia of contralateral limbs and discussed the possible mechanism as well as management. Fractures of medial malleolus usually occur in Hawkins Group III fracture-dislocations in adults. Forced dorsiflexion of talus against the anterior edge of tibia appears to be the accepted common mechanism, despite limited experimental and clinical evidence incriminating axial compression. Fracture of medial malleolus implicates supination. We managed this unusual pattern of injury conservatively. At 15 months, the child was asymptomatic with no radiological evidence of avascular necrosis of body of talus or growth disturbance of distal tibial epiphysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

    DEFF Research Database (Denmark)

    Pincus, Seth H; Moran, Emily; Maresh, Grace

    2012-01-01

    ) is considered the dominant "protective" immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic......Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS...... carbohydrate array technology. The anti-CPS(III) mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we...

  5. A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding

    Science.gov (United States)

    Avery, Adam W.; Crain, Jonathan; Thomas, David D.; Hays, Thomas S.

    2016-01-01

    Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein β-III-spectrin. Here we investigated the molecular consequence of a SCA5 missense mutation that results in a L253P substitution in the actin-binding domain (ABD) of β-III-spectrin. We report that the L253P substitution in the isolated β-III-spectrin ABD causes strikingly high F-actin binding affinity (Kd = 75.5 nM) compared to the weak F-actin binding affinity of the wild-type ABD (Kd = 75.8 μM). The mutation also causes decreased thermal stability (Tm = 44.6 °C vs 59.5 °C). Structural analyses indicate that leucine 253 is in a loop at the interface of the tandem calponin homology (CH) domains comprising the ABD. Leucine 253 is predicted to form hydrophobic contacts that bridge the CH domains. The decreased stability of the mutant indicates that these bridging interactions are probably disrupted, suggesting that the high F-actin binding affinity of the mutant is due to opening of the CH domain interface. These results support a fundamental role for leucine 253 in regulating opening of the CH domain interface and binding of the ABD to F-actin. This study indicates that high-affinity actin binding of L253P β-III-spectrin is a likely driver of neurodegeneration. PMID:26883385

  6. Using weakly conserved motifs hidden in secretion signals to identify type-III effectors from bacterial pathogen genomes.

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    Xiaobao Dong

    Full Text Available BACKGROUND: As one of the most important virulence factor types in gram-negative pathogenic bacteria, type-III effectors (TTEs play a crucial role in pathogen-host interactions by directly influencing immune signaling pathways within host cells. Based on the hypothesis that type-III secretion signals may be comprised of some weakly conserved sequence motifs, here we used profile-based amino acid pair information to develop an accurate TTE predictor. RESULTS: For a TTE or non-TTE, we first used a hidden Markov model-based sequence searching method (i.e., HHblits to detect its weakly homologous sequences and extracted the profile-based k-spaced amino acid pair composition (HH-CKSAAP from the N-terminal sequences. In the next step, the feature vector HH-CKSAAP was used to train a linear support vector machine model, which we designate as BEAN (Bacterial Effector ANalyzer. We compared our method with four existing TTE predictors through an independent test set, and our method revealed improved performance. Furthermore, we listed the most predictive amino acid pairs according to their weights in the established classification model. Evolutionary analysis shows that predictive amino acid pairs tend to be more conserved. Some predictive amino acid pairs also show significantly different position distributions between TTEs and non-TTEs. These analyses confirmed that some weakly conserved sequence motifs may play important roles in type-III secretion signals. Finally, we also used BEAN to scan one plant pathogen genome and showed that BEAN can be used for genome-wide TTE identification. The webserver and stand-alone version of BEAN are available at http://protein.cau.edu.cn:8080/bean/.

  7. Activation of Type I and III Interferon Response by Mitochondrial and Peroxisomal MAVS and Inhibition by Hepatitis C Virus.

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    Silke Bender

    2015-11-01

    Full Text Available Sensing viruses by pattern recognition receptors (PRR triggers the innate immune system of the host cell and activates immune signaling cascades such as the RIG-I/IRF3 pathway. Mitochondrial antiviral-signaling protein (MAVS, also known as IPS-1, Cardif, and VISA is the crucial adaptor protein of this pathway localized on mitochondria, peroxisomes and mitochondria-associated membranes of the endoplasmic reticulum. Activation of MAVS leads to the production of type I and type III interferons (IFN as well as IFN stimulated genes (ISGs. To refine the role of MAVS subcellular localization for the induction of type I and III IFN responses in hepatocytes and its counteraction by the hepatitis C virus (HCV, we generated various functional and genetic knock-out cell systems that were reconstituted to express mitochondrial (mito or peroxisomal (pex MAVS, exclusively. Upon infection with diverse RNA viruses we found that cells exclusively expressing pexMAVS mounted sustained expression of type I and III IFNs to levels comparable to cells exclusively expressing mitoMAVS. To determine whether viral counteraction of MAVS is affected by its subcellular localization we employed infection of cells with HCV, a major causative agent of chronic liver disease with a high propensity to establish persistence. This virus efficiently cleaves MAVS via a viral protease residing in its nonstructural protein 3 (NS3 and this strategy is thought to contribute to the high persistence of this virus. We found that both mito- and pexMAVS were efficiently cleaved by NS3 and this cleavage was required to suppress activation of the IFN response. Taken together, our findings indicate comparable activation of the IFN response by pex- and mitoMAVS in hepatocytes and efficient counteraction of both MAVS species by the HCV NS3 protease.

  8. IM-1662 Attenuates Radiation-Induced Fibroblast Differentiation through Restoration of TGF-beta type III Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyoung; Lim, Min Jin; Lee, Sae Loom; Yun, Yeon Sook; Song, Jie Young [Korea Institue of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2010-05-15

    Although pulmonary fibrosis occurs 5-20% of lung cancer patients who underwent radiotherapy, clinically standard treatment for fibrotic disease has not been developed yet. Among fibrosis mediating factors such as transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), interleukin-13 (IL-13), IL-4, interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF-alpha), TGF-beta is considered as a critical mediator in normal wound healing as well as pathological fibrogenic processes. The TGF-beta transmits signals either directly or indirectly through types I, II and III (TbetaRI, II, and III) receptor complexes and activates downstream Smad signaling. The type III TGF-beta receptor (TbetaRIII or betaglycan) is a transmembrane proteoglycan without a functional kinase domain, and is regarded as a co-receptor to increase the affinity of ligand binding to TbetaRII. In addition, TbetaRIII act as a regulator in cell migration, invasion and cell growth in cancer models. However, in contrast to a great number of studies about TGF-beta ligand and TbetaRII signaling, the relationship between TGF-beta and TbetaRIII (or betaglycan) remains largely unknown. In this study, we searched for a new compound which inhibited TGF-beta responses using cell-based chemical screening and investigated the effects of the novel compound on radiation induced myofibroblast differentiation. We suggest that a novel small molecule, pyrazolopyrimidine compound IM-1662, can act as an anti-fibrotic agent through inhibiting expression of TGF-beta receptor type I and type II whereas, preserving the levels of TbetaRIII which seems to act as a negative regulator in TGF-beta signaling

  9. Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.

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    Hyun-Ja Han

    Full Text Available BACKGROUND: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s involved in the type shift. METHODOLOGY/PRINCIPAL FINDING: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. CONCLUSION/SIGNIFICANCE: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.

  10. Kubas-type hydrogen storage in V(III) polymers using tri- and tetradentate bridging ligands.

    Science.gov (United States)

    Hoang, Tuan K A; Hamaed, Ahmad; Moula, Golam; Aroca, Ricardo; Trudeau, Michel; Antonelli, David M

    2011-04-01

    Oxalic acid, oxamide, glycolic acid, and glycolamide were employed as 2-carbon linkers to synthesize a series of one-dimensional V(III) polymers from trismesityl vanadium(III)·THF containing a high concentration of low-valent metal sites that can be exploited for Kubas binding in hydrogen storage. Synthesized materials were characterized by powder X-ray diffraction (PXRD), nitrogen adsorption (BET), X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (IR), Raman spectroscopy, thermogravimetric analysis, and elemental analysis. Because each of these organic linkers possesses a different number of protons and coordinating atoms, the products in each case were expected to have different stoichiometries with respect to the number of mesityl groups eliminated and also a different geometry about the V(III) centers. For example, the oxalate and glycolate polymers contained residual mesityl groups; however, these could be exchanged with hydride via hydrogenolysis. The highest adsorption capacity was recorded on the product of trismesityl vanadium(III)·THF with oxamide (3.49 wt % at 77 K and 85 bar). As suggested by the high enthalpy of adsorption (17.9 kJ/mol H(2)), a substantial degree of performance of the vanadium metal centers was retained at room temperature (25%), corresponding to a gravimetric adsorption of 0.87 wt % at 85 bar, close to the performance of MOF-177 at this temperature and pressure. This is remarkable given the BET surface area of this material is only 9 m(2)/g. A calculation on the basis of thermogravimetric results provides 0.88 hydrogen molecule per vanadium center under these conditions. Raman studies with H(2) and D(2) showed the first unequivocal evidence for Kubas binding on a framework metal in an extended solid, and IR studies demonstrated H(D) exchange of the vanadium hydride with coordinated D(2). These spectroscopic observations are sufficient to assign the rising trends in isosteric heats of hydrogen adsorption observed

  11. High frequency of methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type III and spa type t030 in Karaj's teaching hospitals, Iran.

    Science.gov (United States)

    Bayat, Bahareh; Zade, Masoumeh Hallaj; Mansouri, Samaneh; Kalantar, Enayat; Kabir, Kourosh; Zahmatkesh, Ehsan; Sepehr, Mohammad Noori; Naseri, Mohammmad Hassan; Darban-Sarokhalil, Davood

    2017-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the most important antibiotic-resistant pathogen in many parts of the world over the past decades. This cross-sectional study was conducted to investigate MRSA isolated between July 2013 and July 2014 in Karaj, Iran. All tested isolates were collected in teaching hospitals from personnel, patients, and surfaces and each MRSA was analyzed by SCCmec and spa typing. Antibiotic susceptibility testing was accomplished by disk diffusion method. Out of 49 MRSA isolates from the Karaj's teaching hospitals, 82%, 10%, and 6% of the isolates were SCCmec types III, II, and I, respectively. The main spa type in this study was spa t030 with frequency as high as 75.5% from intensive care unit (ICU) of the hospitals and high rate of resistance to rifampicin (53%) was found in MRSA isolates. In conclusion, high frequency of spa t030 with SCCmec type III and MRSA phenotype illustrated circulating of one of the antibiotic-resistant strains in ICU of Karaj's teaching hospitals and emphasizes the need for ongoing molecular surveillance, antibiotic susceptibility monitoring, and infection control.

  12. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

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    M Horsey

    2016-07-01

    Full Text Available A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA, confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL, decreased serum B12 levels (56pg/mL, with resultant increased methylmalonic acid (5303nmol/L and hyperhomocysteinemia (131μmol/L, the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD, and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B, defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.

  13. [Medium-term outcome, follow-up, and quality of life in children treated for type III esophageal atresia].

    Science.gov (United States)

    Lepeytre, C; De Lagausie, P; Merrot, T; Baumstarck, K; Oudyi, M; Dubus, J-C

    2013-10-01

    The aim of this study was to evaluate the medium-term outcome (health status, medical and surgical French National Health Authority-recommended follow-up, and quality of life) of children born with type III esophageal atresia (EA). Previous events (during the perinatal period, associated abnormalities, respiratory and digestive complications) of children treated for type III EA at the Marseille university hospitals between 1999 and 2009 were noted. Parents completed a standardized questionnaire concerning the health of their children during the previous year, and a quality-of-life questionnaire (PedsQL 4.0) was also completed by children aged more than 8 years. Among the 68 children treated, 44 responded to our solicitation (mean age, 7.6 years; range, 3-12.8 years). Previous important events were : pneumonia(s) (65%), asthma before the age of 3 years (66%), hospitalization for a respiratory event (45%), fundoplication (20%), and esophageal dilatation (45%). We noted current chronic cough (16%), asthma (30%), dysphagia (39%), and symptomatic gastroesophageal reflux (9%). National guidelines were not respected, except for the surgical indications in children aged less than 6 years. The quality-of-life scores (n=43 children) were similar to healthy controls but were negatively influenced by a gastrostomy procedure (P=0.020), pneumonia (P=0.013), and hospitalization due to a respiratory event (P=0.006) or a digestive event (P=0.010), and also by current asthma (P=0.004). In conclusion, despite recurrent respiratory or digestive symptoms and inadequate recommended follow-up, the quality of life of children treated for type III of EA is good.

  14. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    Directory of Open Access Journals (Sweden)

    Ram Samudrala

    2009-04-01

    Full Text Available The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  15. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

    Energy Technology Data Exchange (ETDEWEB)

    Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

    2009-04-24

    The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, after eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  16. Stochastic gradient boosting classification trees for forest fuel types mapping through airborne laser scanning and IRS LISS-III imagery

    Science.gov (United States)

    Chirici, G.; Scotti, R.; Montaghi, A.; Barbati, A.; Cartisano, R.; Lopez, G.; Marchetti, M.; McRoberts, R. E.; Olsson, H.; Corona, P.

    2013-12-01

    This paper presents an application of Airborne Laser Scanning (ALS) data in conjunction with an IRS LISS-III image for mapping forest fuel types. For two study areas of 165 km2 and 487 km2 in Sicily (Italy), 16,761 plots of size 30-m × 30-m were distributed using a tessellation-based stratified sampling scheme. ALS metrics and spectral signatures from IRS extracted for each plot were used as predictors to classify forest fuel types observed and identified by photointerpretation and fieldwork. Following use of traditional parametric methods that produced unsatisfactory results, three non-parametric classification approaches were tested: (i) classification and regression tree (CART), (ii) the CART bagging method called Random Forests, and (iii) the CART bagging/boosting stochastic gradient boosting (SGB) approach. This contribution summarizes previous experiences using ALS data for estimating forest variables useful for fire management in general and for fuel type mapping, in particular. It summarizes characteristics of classification and regression trees, presents the pre-processing operation, the classification algorithms, and the achieved results. The results demonstrated superiority of the SGB method with overall accuracy of 84%. The most relevant ALS metric was canopy cover, defined as the percent of non-ground returns. Other relevant metrics included the spectral information from IRS and several other ALS metrics such as percentiles of the height distribution, the mean height of all returns, and the number of returns.

  17. Two-Higgs-Doublet type-II and -III models and $t\\to c h$ at the LHC

    CERN Document Server

    Arhrib, A; Chen, Chuan-Hung; Gomez-Bock, M; Semlali, S

    2015-01-01

    Based on the updated $8$ TeV LHC data for the Higgs searches, we study the constraints of generic two-Higgs-doublet model (2HDM) type-III and the impacts of the new Yukawa couplings. For comparisons, we revisit the analysis in 2HDM type-II. For understanding the influence of all involving free parameters and realizing their correlations, we employ $\\chi$-square fitting approach by including theoretical and experimental constraints, such as $B\\to X_s \\gamma$, $B_q-\\bar B_q$ mixing, S, T and U oblique parameters, the production of standard model Higgs and its decay to $\\gamma\\gamma$, $WW^*/ZZ^*$, $\\tau^+ \\tau^-$, etc. The errors of analysis are taken at $68\\%$, $95.5\\%$ and $99.7\\%$ confidence level. Due to the new Yukawa couplings being associated with $\\cos(\\alpha-\\beta)$ and $\\sin(\\alpha-\\beta)$, we find that the allowed regions for $\\sin\\alpha$ and $\\tan\\beta$ in type-III could be broader when the dictated parameter $\\chi_F$ is positive; however, for negative $\\chi_F$, the limits are more strict than those ...

  18. Crystal structures of type III{sub H} NAD-dependent D-3-phosphoglycerate dehydrogenase from two thermophiles

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Pampa, K.J. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Manjula, M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Hemantha Kumar, G. [Department of Studies in Computer Science, University of Mysore, Mysore 570 006 (India); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Lokanath, N.K., E-mail: lokanath@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India)

    2014-08-15

    Highlights: • Determined the crystal structures of PGDH from two thermophiles. • Monomer is composed of nucleotide binding domain and substrate binding domain. • Crystal structures of type III{sub H} PGDH. - Abstract: In the L-Serine biosynthesis, D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes the inter-conversion of D-3-phosphoglycerate to phosphohydroxypyruvate. PGDH belongs to 2-hydroxyacid dehydrogenases family. We have determined the crystal structures of PGDH from Sulfolobus tokodaii (StPGDH) and Pyrococcus horikoshii (PhPGDH) using X-ray diffraction to resolution of 1.77 Å and 1.95 Å, respectively. The PGDH protomer from both species exhibits identical structures, consisting of substrate binding domain and nucleotide binding domain. The residues and water molecules interacting with the NAD are identified. The catalytic triad residues Glu-His-Arg are highly conserved. The residues involved in the dimer interface and the structural features responsible for thermostability are evaluated. Overall, structures of PGDHs with two domains and histidine at the active site are categorized as type III{sub H} and such PGDHs structures having this type are reported for the first time.

  19. H-1 and N-15 resonance assignment of the second fibronectin type III module of the neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Kiselyov, Vladislav V; Berezin, Vladimir; Bock, Elisabeth;

    2008-01-01

    We report here the NMR assignment of the second fibronectin type III module of the neural cell adhesion molecule (NCAM). This module has previously been shown to interact with the fibroblast growth factor receptor (FGFR), and the FGFR-binding site was mapped by NMR to the FG-loop region...... of the module. The FG-loop region also contains a putative nucleotide-binding motif, which was shown by NMR to interact with ATP. Furthermore, ATP was demonstrated to inhibit binding of the second F3 module of NCAM to FGFR....

  20. Arabidopsis HFR1 Is a Potential Nuclear Substrate Regulated by the Xanthomonas Type III Effector XopD Xcc8004

    OpenAIRE

    Choon Meng Tan; Meng-Ying Li; Pei-Yun Yang; Shu Heng Chang; Yi-Ping Ho; Hong Lin; Wen-Ling Deng; Jun-Yi Yang

    2015-01-01

    XopD Xcc8004, a type III effector of Xanthomonas campestris pv. campestris (Xcc) 8004, is considered a shorter version of the XopD, which lacks the N-terminal domain. To understand the functions of XopD Xcc8004, in planta, a transgenic approach combined with inducible promoter to analyze the effects of XopD Xcc8004 in Arabidopsis was done. Here, the expression of XopD Xcc8004, in Arabidopsis elicited the accumulation of host defense-response genes. These molecular changes were dependent on sa...

  1. Progressive non-infectious anterior vertebral fusion in a baby with Saethre-Chotzen-acrocephalosyndactyly type III syndrome

    OpenAIRE

    2015-01-01

    We report on a 3-months old baby of Austrian origin and product of non-consanguineous parents. Abnormal craniofacial contour was the main deformity. The overall clinico-radiographic features were consistent with Saether-Chotzen-acrocephalosyndactyly type III syndrome. Bi-directional sequencing of the exon 8 and of the FGFR3-genes, exons 7 of FGFR3 (Fibroblast growth factor receptor3) genes, the exon 5 of the FGFR1 gene, revealed no mutations. Sagittal MRI imaging of the spine showed anterior ...

  2. Hepatocyte Growth Factor Suppresses Transforming Growth Factor-Beta-1 and Type III Collagen in Human Primary Renal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Shan Mou

    2009-11-01

    Full Text Available Tubulointerstitial changes in the diabetic kidney correlate closely with renal fibrosis, and transforming growth factor-beta-1 (TGF-β1 is thought to play a key role in this process. In contrast, hepatocyte growth factor (HGF has shown therapeutic effects on injured renal tubules in animal models. This study was undertaken to test the hypothesis that the preventive effects of HGF may result from interventions in TGF-β1-mediated signaling and collagen III secretion. We examined the expression of HGF/HGF receptor (c-Met and TGF-β1 in renal fibroblasts at multiple time points. The effects of recombinant human HGF on TGF-β1 expression were studied by RT-PCR and Western blotting, and the levels of collagen III were measured by ELISA. In the high-glucose condition, the expression of HGF and c-Met in renal fibroblasts was detected as early as 6 hours following cell culture while the level of TGF-β1 peaked at 96 hours. The addition of recombinant human HGF to the culture media dose-dependently inhibited TGF-β1 mRNA expression and reduced collagen III secretion by 34%. These results indicate that, during hyperglycemia, HGF inhibits TGF-β1 signaling and type III collagen activation in interstitial fibroblasts. Furthermore, we should recognize that changes in the balance between HGF and TGF-β1 might be decisive in the pathogenesis of chronic renal fibrosis. Therefore, administration of HGF to restore this balance may offer a novel therapeutic intervention in managing renal fibrogenesis in diabetic nephropathy.

  3. Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: a meta-analysis

    National Research Council Canada - National Science Library

    Zhang, Yan; Li, Lixiang; Guo, Chuanguo; Mu, Dan; Feng, Bingcheng; Zuo, Xiuli; Li, Yanqing

    2016-01-01

    .... The aim of the current study was to assess the efficacy of different probiotic types, doses and treatment durations in IBS patients diagnosed by Rome III criteria via a meta-analysis of randomized controlled trials (RCTs...

  4. Design guide for Category III reactors: pool type reactors. [US DOE

    Energy Technology Data Exchange (ETDEWEB)

    Brynda, W J; Lobner, P R; Powell, R W; Straker, E A

    1978-11-01

    The Department of Energy (DOE) in the ERDA Manual requires that all DOE-owned reactors be sited, designed, constructed, modified, operated, maintained, and decommissioned in a manner that gives adequate consideration to health and safety factors. Specific guidance pertinent to the safety of DOE-owned reactors is found in Chapter 0540 of the ERDA Manual. The purpose of this Design Guide is to provide additional guidance to aid the DOE facility contractor in meeting the requirement that the siting, design, construction, modification, operation, maintenance, and decommissioning of DOE-owned reactors be in accordance with generally uniform standards, guides, and codes which are comparable to those applied to similar reactors licensed by the Nuclear Regulatory Commission (NRC). This Design Guide deals principally with the design and functional requirement of Category III reactor structures, components, and systems.

  5. The matlockite-type praseodymium(III oxide bromide PrOBr

    Directory of Open Access Journals (Sweden)

    Pia Talmon-Gros

    2011-12-01

    Full Text Available The crystal structure of the praseodymium(III oxide bromide, PrOBr, can be best described with layers of agglomerated square antiprisms [PrO4Br4]9−. These slabs are stacked along the c axis and linked via two different secondary contacts between Pr3+ and Br−. The Pr3+ cations occupy the Wyckoff site 2c with 4mm symmetry and carry four O2− anions as well as four primary Br− anions, yielding a coordination number of 8. While the Br− anions exhibit the same site symmetry as the Pr3+ cations, the oxide anions are located at the Wyckoff position 2a with site symmetry overline{4}m2 and have four Pr3+ cations as neighbours, defining a tetrahedron.

  6. Self-assembly synthesis, structural features, and photophysical properties of dilanthanide complexes derived from a novel amide type ligand: energy transfer from Tb(III) to Eu(III) in a heterodinuclear derivative.

    Science.gov (United States)

    Gao, Cunji; Kirillov, Alexander M; Dou, Wei; Tang, Xiaoliang; Liu, Liangliang; Yan, Xuhuan; Xie, Yujie; Zang, Peixian; Liu, Weisheng; Tang, Yu

    2014-01-21

    A novel amide type ligand benzyl-N,N-bis[(2'-furfurylaminoformyl)phenoxyl)ethyl]-amine (L) has been designed and applied for the self-assembly generation of homodinuclear lanthanide coordination compounds [Ln2(μ2-L)2(NO3)6(EtOH)2] [Ln = Eu (1), Tb (2), and Gd (3)] and a heterodinuclear derivative [EuTb(μ2-L)2(NO3)6(EtOH)2] (4). All the complexes have been characterized by the X-ray single-crystal diffraction analyses. They are isostructural, crystallize in a monoclinic space group P21/c, and form [2 + 2] rectangular macrocycle structures. Compound 4 is the first example of a [2 + 2] rectangular macrocycle heterodinuclear EuTb complex assembled from an amide type ligand. In 4, the discrete 0D dimeric [EuTb(μ2-L)2(NO3)6(EtOH)2] units are extended, via the multiple N-H···O hydrogen bonds, into a 2D supramolecular network that has been topologically classified as a uninodal 4-connected underlying net with the sql [Shubnikov tetragonal plane net] topology. The triplet state ((3)ππ*) of L studied by the Gd(III) complex 3 demonstrated that the ligand beautifully populates Tb(III) emission (Φ = 52%), whereas the corresponding Eu(III) derivative 1 shows weak luminescence efficiency (Φ = 0.7%) because the triplet state of L has a poor match with (5)D1 energy level of Eu(III). Furthermore, the photoluminescent properties of heterodinuclear complex 4 have been compared with those of the analogous homodinuclear compounds. The quantum yield and lifetime measurements prove that energy transfer from Tb(III) to Eu(III) is being achieved, namely, that the Tb(III) center is also acting to sensitize the Eu(III) and enhancing Eu(III) emission in 4.

  7. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Science.gov (United States)

    Hogan, P; Oliver, T

    2016-01-01

    Summary A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases. Learning points A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome. Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease. Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism. PMID:27482386

  8. The domain of attraction of the α-sun operator for type II and type III distributions

    NARCIS (Netherlands)

    Hooghiemstra, G.; Greenwood, P.E.

    1996-01-01

    Let be a sequence of independent random variables with common distribution and define the iteration , , . We denote by the domain of maximal attraction of , the extreme value distribution of the first type. Greenwood and Hooghiemstra showed in 1991 that for there exist norming constants and such tha

  9. Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt.

    Science.gov (United States)

    Freeman, James J; Schreiner, Ceinwen A; Beazley, S; Burnett, Donald M; Clark, Charles R; Mahagaokar, Suneeta; Parker, Craig M; Stewart, Christopher W; Swanson, Mark S; Arp, Earl W

    2011-10-01

    Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 μg applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 μg, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.

  10. Clonal structure of Trypanosoma cruzi Colombian strain (biodeme Type III: biological, isoenzymic and histopathological analysis of seven isolated clones

    Directory of Open Access Journals (Sweden)

    Camandaroba Edson Luiz Paes

    2001-01-01

    Full Text Available The clonal structure of the Colombian strain of Trypanosoma cruzi, biodeme Type III and zymodeme 1, was analyzed in order to characterize its populations and to establish its homogeneity or heterogeneity. Seven isolated clones presented the basic characteristics of Biodeme Type III, with the same patterns of parasitemic curves, tissue tropism to skeletal muscle and myocardium, high pathogenicity with extensive necrotic-inflammatory lesions from the 20th to 30th day of infection. The parental strain and its clones C1, C3, C4 and C6, determined the higher levels of parasitemia, 20 to 30 days of infection, with high mortality rate up to 30 days (79 to 100%; clones C2, C5 and C7 presented lower levels of parasitemia, with low mortality rates (7.6 to 23%. Isoenzymic patterns, characteristic of zymodeme 1, (Z1 were similar for the parental strain and its seven clones. Results point to a phenotypic homogeneity of the clones isolated from the Colombian strain and suggest the predominance of a principal clone, responsible for the biological behavior of the parental strain and clones.

  11. Axonal Type III Nrg1 Controls Glutamate Synapse Formation and GluA2 Trafficking in Hippocampal-Accumbens Connections

    Science.gov (United States)

    Akmentin, Wendy

    2017-01-01

    Abstract Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs). Reduced expression of axonal type III Nrg1 along vHipp projections also decreases functional synaptic vesicle (SV) clustering and vesicular trafficking to presynaptic vHipp axonal terminals. These findings suggest that Nrg1/ErbB signaling modulate glutamatergic transmission via both pre- and postsynaptic mechanisms. PMID:28275713

  12. Serum type III procollagen peptide in patients with Pneumocystis carinii infection. The Copenhagen-Amsterdam PCP-Prednisolone Study Group

    DEFF Research Database (Denmark)

    Bentsen, K D; Nielsen, T L; Eaftinck Schattenkerk, J K

    1993-01-01

    Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investi......Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders....... To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group...... steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS...

  13. Functional insights into the Shigella type III needle tip IpaD in secretion control and cell contact.

    Science.gov (United States)

    Schiavolin, Lionel; Meghraoui, Alaeddine; Cherradi, Youness; Biskri, Latéfa; Botteaux, Anne; Allaoui, Abdelmounaaïm

    2013-04-01

    Type III secretion apparatus (T3SA) are complex nanomachines that insert a translocation pore into the host cell membrane through which effector proteins are injected into the cytosol. In Shigella, the pore is inserted by a needle tip complex that also controls secretion. IpaD is the key protein that rules the composition of the tip complex before and upon cell contact or Congo red (CR) induction. However, how IpaD is involved in secretion control and translocon insertion remains not fully understood. Here, we report the phenotypic analysis of 20 10-amino acids deletion variants all along the coiled-coil and the central domains of IpaD (residues 131-332). Our results highlight three classes of T3S phenotype; (i) wild-type secretion, (ii) constitutive secretion of all classes of effectors, and (iii) constitutive secretion of translocators and early effectors, but not of late effectors. Our data also suggest that the composition of the tip complex defines both the T3SA inducibility state and late effectors secretion. Finally, we shed light on a new aspect regarding the contact of the needle tip with cell membrane by uncoupling the Shigella abilities to escape macrophage vacuole, and to insert the translocation pore or to invade non-phagocytic cells.

  14. Re-evaluating the kinetics of ATP hydrolysis during initiation of DNA sliding by Type III restriction enzymes.

    Science.gov (United States)

    Tóth, Júlia; Bollins, Jack; Szczelkun, Mark D

    2015-12-15

    DNA cleavage by the Type III restriction enzymes requires long-range protein communication between recognition sites facilitated by thermally-driven 1D diffusion. This 'DNA sliding' is initiated by hydrolysis of multiple ATPs catalysed by a helicase-like domain. Two distinct ATPase phases were observed using short oligoduplex substrates; the rapid consumption of ∼10 ATPs coupled to a protein conformation switch followed by a slower phase, the duration of which was dictated by the rate of dissociation from the recognition site. Here, we show that the second ATPase phase is both variable and only observable when DNA ends are proximal to the recognition site. On DNA with sites more distant from the ends, a single ATPase phase coupled to the conformation switch was observed and subsequent site dissociation required little or no further ATP hydrolysis. The overall DNA dissociation kinetics (encompassing site release, DNA sliding and escape via a DNA end) were not influenced by the second phase. Although the data simplifies the ATP hydrolysis scheme for Type III restriction enzymes, questions remain as to why multiple ATPs are hydrolysed to prepare for DNA sliding.

  15. Dissociation from DNA of Type III Restriction-Modification enzymes during helicase-dependent motion and following endonuclease activity.

    Science.gov (United States)

    Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D

    2012-08-01

    DNA cleavage by the Type III Restriction-Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼ 200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can 'turnover', albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. 'DNA sliding').

  16. The inner rod protein controls substrate switching and needle length in a Salmonella type III secretion system.

    Science.gov (United States)

    Lefebre, Matthew D; Galán, Jorge E

    2014-01-14

    Type III secretion machines are essential for the biology of many bacteria that are pathogenic or symbiotic for animals, plants, or insects. They exert their function by delivering bacterial effector proteins into target eukaryotic cells. The core component of these machines is the needle complex, a multiprotein structure that spans the bacterial envelope and serves as a conduit for proteins that transit this secretion pathway. The needle complex is composed of a multiring base embedded in the bacterial envelope and a filament-like structure, the needle, that projects from the bacterial surface and is linked to the base by the inner rod. Assembly of the needle complex proceeds in a step-wise fashion that is initiated by the assembly of the base and is followed by the export of the building subunits for the needle and inner rod substructures. Once assembled, the needle complex reprograms its specificity and becomes competent for the secretion of effector proteins. Here through genetic, biochemical, and electron microscopy analyses of the Salmonella inner rod protein subunit PrgJ we present evidence that the assembly of the inner rod dictates the timing of substrate switching and needle length. Furthermore, the identification of mutations in PrgJ that specifically alter the hierarchy of protein secretion provides additional support for a complex role of the inner rod substructure in type III secretion.

  17. Weak Interactions between Salmonella enterica FlhB and Other Flagellar Export Apparatus Proteins Govern Type III Secretion Dynamics.

    Directory of Open Access Journals (Sweden)

    Jonathan L McMurry

    Full Text Available The bacterial flagellum contains its own type III secretion apparatus that coordinates protein export with assembly at the distal end. While many interactions among export apparatus proteins have been reported, few have been examined with respect to the differential affinities and dynamic relationships that must govern the mechanism of export. FlhB, an integral membrane protein, plays critical roles in both export and the substrate specificity switching that occurs upon hook completion. Reported herein is the quantitative characterization of interactions between the cytoplasmic domain of FlhB (FlhBC and other export apparatus proteins including FliK, FlhAC and FliI. FliK and FlhAC bound with micromolar affinity. KD for FliI binding in the absence of ATP was 84 nM. ATP-induced oligomerization of FliI induced kinetic changes, stimulating fast-on, fast-off binding and lowering affinity. Full length FlhB purified under solubilizing, nondenaturing conditions formed a stable dimer via its transmembrane domain and stably bound FliH. Together, the present results support the previously hypothesized central role of FlhB and elucidate the dynamics of protein-protein interactions in type III secretion.

  18. Crystal structure of the Csm3-Csm4 subcomplex in the type III-A CRISPR-Cas interference complex.

    Science.gov (United States)

    Numata, Tomoyuki; Inanaga, Hideko; Sato, Chikara; Osawa, Takuo

    2015-01-30

    Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci play a pivotal role in the prokaryotic host defense system against invading genetic materials. The CRISPR loci are transcribed to produce CRISPR RNAs (crRNAs), which form interference complexes with CRISPR-associated (Cas) proteins to target the invading nucleic acid for degradation. The interference complex of the type III-A CRISPR-Cas system is composed of five Cas proteins (Csm1-Csm5) and a crRNA, and targets invading DNA. Here, we show that the Csm1, Csm3, and Csm4 proteins from Methanocaldococcus jannaschii form a stable subcomplex. We also report the crystal structure of the M. jannaschii Csm3-Csm4 subcomplex at 3.1Å resolution. The complex structure revealed the presence of a basic concave surface around their interface, suggesting the RNA and/or DNA binding ability of the complex. A gel retardation analysis showed that the Csm3-Csm4 complex binds single-stranded RNA in a non-sequence-specific manner. Csm4 structurally resembles Cmr3, a component of the type III-B CRISPR-Cas interference complex. Based on bioinformatics, we constructed a model structure of the Csm1-Csm4-Csm3 ternary complex, which provides insights into its role in the Csm interference complex.

  19. Comparison of the Tight Rope Technique and Clavicular Hook Plate for the Treatment of Rockwood Type III Acromioclavicular Joint Dislocation.

    Science.gov (United States)

    Cai, Leyi; Wang, Te; Lu, Di; Hu, Wei; Hong, Jianjun; Chen, Hua

    2017-04-12

    Acromioclavicular joint dislocation is one of the most common shoulder problems and may lead to instability or degenerative changes. The aim of this study was to compare the clinical outcomes of the Tight Rope system and clavicular hook plate for Rockwood type III acromioclavicular joint dislocation in adults. This was a prospective, randomized study in a hospital setting. From January 2012 to December 2014, 69 patients with type III injury were reviewed. Patients were randomly divided into two groups: Group A was treated using the TightRope system and Group B with the clavicular hook plate. All participants were followed up for 12 months. Clinical outcomes, radiological results and postoperative complications were recorded. The length of incision was significantly shorter in Goup A than that in Group B. The blood loss of surgery was significantly less in the Group A. Significant difference could be found between the two groups regarding the Visual Analogue Scale scores one day after surgery, at the 3 and 12 months follow-up. There were no differences according to the improvement of the Constant-Murley score and the coracoclavicular distance between the groups. The two groups have similar clinical and radiological outcomes. Both treatments could relieve the pain of dislocation, improve the function of Acromioclavicular joint and rectify the coracoclavicular distance measured in plain films. However, the TightRope system exhibited some advantages in terms of length of incision, blood loss of surgery, the pain postoperatively and no need for a second surgery.

  20. IgG kappa monoclonal gammopathy of undetermined significance presenting as acquired type III Von Willebrand syndrome.

    Science.gov (United States)

    Howard, Christin R; Lin, Tara L; Cunningham, Mark T; Lipe, Brea C

    2014-09-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated with hematoproliferative disorders, autoimmune conditions, neoplasia and cardiovascular disorders that often present a diagnostic challenge. Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common causes of AVWS that typically presents later in life with mucocutaneous or postsurgical bleeding and multimers consistent with type I or II von Willebrand disease (VWD). Here, we present the case of a patient with a 32-year history of type III VWD that was ultimately found to be AVWS related to an IgG MGUS. In this case report, we highlight the diagnostic challenges of AVWS to ensure proper identification and potentially lifesaving treatment of this rare disorder.

  1. The Galactic O-Star Spectroscopic Survey (GOSSS). III. 142 Additional O-type Systems.

    Science.gov (United States)

    Maíz Apellániz, J.; Sota, A.; Arias, J. I.; Barbá, R. H.; Walborn, N. R.; Simón-Díaz, S.; Negueruela, I.; Marco, A.; Leão, J. R. S.; Herrero, A.; Gamen, R. C.; Alfaro, E. J.

    2016-05-01

    This is the third installment of the Galactic O-Star Spectroscopic Survey (GOSSS), a massive spectroscopic survey of Galactic O stars, based on new homogeneous, high signal-to-noise ratio, R ˜ 2500 digital observations selected from the Galactic O-Star Catalog. In this paper, we present 142 additional stellar systems with O stars from both hemispheres, bringing the total of O-type systems published within the project to 590. Among the new objects, there are 20 new O stars. We also identify 11 new double-lined spectroscopic binaries, 6 of which are of O+O type and 5 of O+B type, and an additional new tripled-lined spectroscopic binary of O+O+B type. We also revise some of the previous GOSSS classifications, present some egregious examples of stars erroneously classified as O-type in the past, introduce the use of luminosity class IV at spectral types O4-O5.5, and adapt the classification scheme to the work of Arias et al. The GOSSS spectroscopic data in this article were gathered with five facilities: the 1.5 m Telescope at the Observatorio de Sierra Nevada (OSN), the 2.5 m du Pont Telescope at Las Campanas Observatory (LCO), the 3.5 m Telescope at Calar Alto Observatory (CAHA), and the 4.2 m William Herschel Telescope (WHT) and 10.4 m Gran Telescopio Canarias (GTC) at Observatorio del Roque de los Muchachos (ORM).

  2. The Galactic O-Star Spectroscopic Survey (GOSSS). III. 142 additional O-type systems

    CERN Document Server

    Apellániz, J Maíz; Arias, J I; Barbá, R H; Walborn, N R; Simón-Díaz, S; Negueruela, I; Marco, A; Leão, J R S; Herrero, A; Gamen, R C; Alfaro, E J

    2016-01-01

    This is the third installment of GOSSS, a massive spectroscopic survey of Galactic O stars, based on new homogeneous, high signal-to-noise ratio, R~2500 digital observations selected from the Galactic O-Star Catalog (GOSC). In this paper we present 142 additional stellar systems with O stars from both hemispheres, bringing the total of O-type systems published within the project to 590. Among the new objects there are 20 new O stars. We also identify 11 new double-lined spectroscopic binaries (SB2s), of which 6 are of O+O type and 5 of O+B type, and an additional new tripled-lined spectroscopic binary (SB3) of O+O+B type. We also revise some of the previous GOSSS classifications, present some egregious examples of stars erroneously classified as O-type in the past, introduce the use of luminosity class IV at spectral types O4-O5.5, and adapt the classification scheme to the work of Arias et al. (2016).

  3. The noncanonical type III secretion system of Xanthomonas translucens pv. graminis is essential for forage grass infection.

    Science.gov (United States)

    Wichmann, Fabienne; Vorhölter, Frank-Jörg; Hersemann, Lena; Widmer, Franco; Blom, Jochen; Niehaus, Karsten; Reinhard, Sonja; Conradin, Constanze; Kölliker, Roland

    2013-08-01

    Xanthomonas translucens pv. graminis (Xtg) is a gammaproteobacterium that causes bacterial wilt on a wide range of forage grasses. To gain insight into the host-pathogen interaction and to identify the virulence factors of Xtg, we compared a draft genome sequence of one isolate (Xtg29) with other Xanthomonas spp. with sequenced genomes. The type III secretion system (T3SS) encoding a protein transport system for type III effector (T3E) proteins represents one of the most important virulence factors of Xanthomonas spp. In contrast with other Xanthomonas spp. assigned to clade 1 on the basis of phylogenetic analyses, we identified an hrp (hypersensitive response and pathogenicity) gene cluster encoding T3SS components and a representative set of 35 genes encoding putative T3Es in the genome of Xtg29. The T3SS was shown to be divergent from the hrp gene clusters of other sequenced Xanthomonas spp. Xtg mutants deficient in T3SS regulating and structural genes were constructed to clarify the role of the T3SS in forage grass colonization. Italian ryegrass infection with these mutants led to significantly reduced symptoms (P < 0.05) relative to plants infected with the wild-type strain. This showed that the T3SS is required for symptom evocation. In planta multiplication of the T3SS mutants was not impaired significantly relative to the wild-type, indicating that the T3SS is not required for survival until 14 days post-infection. This study represents the first major step to understanding the bacterial colonization strategies deployed by Xtg and may assist in the identification of resistance (R) genes in forage grasses.

  4. Type 1 AGN at low z. III. The optical narrow line ratios

    CERN Document Server

    Stern, Jonathan

    2012-01-01

    We present the optical narrow line ratios in an SDSS based sample of 3,175 broad Ha selected type 1 AGN, and explore their positions in the BPT diagrams as a function of the AGN and the host properties. We find the following: 1. The luminosities of all measured narrow lines (Ha, Hb, [OIII], [NII], [SII], [OI]) show a Baldwin relation relative to the broad Ha luminosity L_bHa, with slopes in the range of 0.53-0.72. 2. About 20% of the type 1 AGN reside within the `Composite' and `SF' regions of the BPT diagrams. These objects also show excess narrow Ha and UV luminosities, for their L_bHa, consistent with contribution from star formation which dominates the narrow lines emission, as expected from their positions in the BPT diagrams. 3. The type 1 which reside within the AGN region in the BPT diagrams, are offset to lower [SII]/Ha and [NII]/Ha luminosity ratios, compared to type 2 AGN. This offset is a selection effect, related to the lower AGN/host luminosity selection of the type 2 AGN selected from the SDSS ...

  5. Type III monteggia injury with ipsilateral type II Salter Harris injury of the distal radius and ulna in a child: a case report.

    Science.gov (United States)

    Williams, Huw L M; Madhusudhan, Thayur R; Sinha, Amit

    2014-03-17

    Although previously reported, ipsilateral Monteggia fracture dislocation and distal radius fracture in a child is still a rare occurrence. A full clinical examination may be difficult but should not be ignored. Full length forearm radiographs are ideal but proper limb positioning may be difficult. The injury pattern can be easily missed. A five-year-old right hand dominant Caucasian male presented with a history of fall on outstretched hand. Clinical examination was difficult and X-rays confirmed type III Monteggia fracture with an ipsilateral Type II Salter Harris injury of the distal radius and ulna. This report highlights the need for relevant examination of the wrist and elbow in young children. Appropriate radiographs must also be performed to prevent missing these injuries.

  6. DETERMINATION OF CORROSION INHIBITOR CRITERIA FOR TYPE III/IIIA TANKS DURING SALT DISSOLUTION OPERATIONS SUMMARY DOCUMENT

    Energy Technology Data Exchange (ETDEWEB)

    Mickalonis, J.; Wiersma, B.; Garcia-Diaz, B.

    2009-10-01

    Dissolution of salt from Type III/IIIA waste tanks at the Savannah River Site may create solutions with inhibitor concentrations below those currently required (0.6M OH{sup -} and 1.1M OH{sup -} + NO{sub 2}{sup -}) per the Corrosion Control Program for high nitrate salt solutions (5.5 to 8.5M NO{sub 3}{sup -}). An experimental program was conducted to evaluate the corrosion susceptibility of grade A537 carbon steel for waste simulants containing 4.5-8.5M NaNO{sub 3} with maximum inhibitor concentrations of 0.6M NaOH and 0.2M NaNO{sub 2}. These maximum inhibitor concentrations used in this program are at a reduced level from those currently required. Current requirements were initially established for the Types I, II and IV tanks made of A285 carbon steel. The experimental program involved corrosion testing to evaluate the pitting and stress corrosion stress corrosion cracking (SCC) susceptibility of the Type III/IIIA waste tank materials. The program was conducted in two phases; the results of the first phase were reported previously (WSRC-STI-2006-00029). In this second phase, the corrosion specimens were modified to represent the 'as-fabricated' condition of the tank wall, and included specimens with mill scale, ground welds and stress-relief heat treatments. The complete description of the corrosion testing and the results are reported herein. The collective corrosion test results for A537 carbon steel in high nitrate waste simulants (4.5 - 8.5M) with the maximum inhibitor concentrations of 0.6M NaOH and 0.2M NaNO{sub 2} were as follows: (1) In long-term non-polarized U-bend testing, heat treatment, similar to the waste tank stress relief regime, reduced the incidence of cracking over the 18-month test period. Vapor space SCC was found to initiate on non-heat treated U-bend coupons. (2) In polarized U-bend testing, cracking occurred on U-bend coupons that had welds prepared similar to those in the waste tanks, i.e. ground and heat treated. (3) In

  7. High Dispersion Spectroscopy of Solar-type Superflare Stars. III. Lithium Abundances

    CERN Document Server

    Honda, Satoshi; Maehara, Hiroyuki; Notsu, Shota; Shibayama, Takuya; Nogami, Daisaku; Shibata, Kazunari

    2015-01-01

    We report on the abundance analysis of Li in solar-type (G-type main sequence) superflare stars which were found by the analysis of Kepler photometric data. Li is a key element to understand the evolution of the stellar convection zone which reflects the age of solar-type stars. We performed the high dispersion spectroscopy of solar-type superflare stars with Subaru/HDS, and confirmed that 34 stars show no evidence of binarity in our previous study. In this study, we derived the Li abundances of these 34 objects. We investigate correlations of Li abundance with stellar atmospheric parameters, rotational velocity, and superflare activities to understand the nature of superflare stars and the possibility of the nucleosynthesis of Li by superflares. We confirm the large dispersion in the Li abundance, and the correlation with stellar parameters is not seen. As compared with the Li abundance in Hyades cluster which is younger than the Sun, it is suggested that half of the observed stars are younger than Hyades cl...

  8. Type III interferon protects swine against foot-and-mouth disease

    Science.gov (United States)

    In recent years we have developed novel strategies to control foot-and-mouth disease (FMD) including the use of biotherapeutics such as interferons (IFN) delivered by a replication-defective human adenovirus type 5 (Ad5). Swine can be sterilely protected after vaccination with an Ad5 that encodes po...

  9. Galaxy populations in the Antlia cluster - III. Properties of faint early-type galaxies

    CERN Document Server

    Castelli, Analia V Smith; Faifer, Favio R; Bassino, Lilia P; Richtler, Tom; Romero, Gisela A; Calderon, Juan Pablo; Caso, Juan Pablo

    2011-01-01

    (Abridge) We present a new analysis of the early-type galaxy population in the central region of the Antlia cluster, focusing on the faint systems like dwarf ellipticals (dE) and dwarf spheroidals (dSph). We confirm 22 early-type galaxies as Antlia members, using GEMINI-GMOS and MAGELLAN-MIKE spectra. Among them, 2 belong to the rare type of compact ellipticals (cE), and 5 are new faint dwarfs that had never been catalogued before. In addition, we present 16 newly identified low surface brightness galaxy candidates, almost half of them displaying morphologies consistent with being Antlia's counterparts of Local Group dSphs, that extend the faint luminosity limit of our study down to MB = -10.1 (BT = 22.6) mag. We built an improved CMR in the Washington photometric system, i.e. integrated T1 magnitudes versus (C - T1) colours, which extends \\sim 4 mag faintwards the limit of spectroscopically confirmed Antlia members. When only confirmed early-type members are considered, this relation extends over 10 mag in l...

  10. Acute downregulation of Type II and Type III iodothyronine deiodinases by photoperiod in peripubertal male and female Siberian hamsters.

    Science.gov (United States)

    Kampf-Lassin, August; Prendergast, Brian J

    2013-11-01

    Availability of the thyroid hormone triiodothyronine (T3) in the mediobasal hypothalamus plays a central role in seasonal reproductive responses to photoperiod. Across many vertebrates, Type 2 iodothyronine deiodinase (DIO2) is elevated under reproductively stimulatory long days (LD) and synthesizes the conversion of thyroxine to T3; Type 3 iodothyronine deiodinase (DIO3) reduces T3 production and signaling, and is upregulated under reproductively-inhibitory short days (SD). In Siberian hamsters, regulation of hypothalamic T3 is dominated by dio3 expression, whereas dio2 expression is less-consistently affected by photoperiod. In adult hamsters, changes in deiodinase mRNA expression typically require several weeks to manifest, but it is not known whether or how quickly these mechanisms are engaged during the rapid responses to photoperiod observed in young, peri-pubertal hamsters. This experiment tested the hypotheses that (1) deiodinase responses to photoperiod are accelerated in juvenile hamsters and (2) photoperiodic downregulation of deiodinase expression occurs more rapidly than upregulation. Hypothalamic dio2 and dio3 mRNA expression was quantified in male and female Siberian hamsters that were weaned on postnatal day 18 (PND 18) into SD or remained in their natal LD, and on PND 31 were exposed to a single long or short day. In SD males and females, a single long day inhibited dio3 mRNA expression, but did not increase dio2 mRNA. In LD males, a single short day rapidly inhibited dio2 mRNA expression, but did not stimulate expression of dio3 mRNA. Downregulation of dio2 and dio3 mRNAs precedes gonadotrophin responses to day length. Rapid photoperiodic inhibition of deiodinase mRNAs may initiate changes in thyroid hormone signaling in advance of longer-term, melatonin-dependent, responses.

  11. Improvement of Cardiomyopathy After High-Fat Diet in Two Siblings with Glycogen Storage Disease Type III.

    Science.gov (United States)

    Brambilla, Alessandra; Mannarino, Savina; Pretese, Roberta; Gasperini, Serena; Galimberti, Cinzia; Parini, Rossella

    2014-01-01

    Glycogenosis type III (GSD III) is an autosomal recessive disorder due to amylo-1,6-glucosidase deficiency. This disease causes limit dextrin storage in affected tissues: liver, skeletal muscles, and heart in GSD IIIa and only liver in GSD IIIb. Cardiomyopathy is quite frequent in GSD IIIa with variable severity and progression of manifestations. It is not clear if diet manipulation may interfere with cardiomyopathy's progression. Recent case reports showed improvement of cardiomyopathy following a ketogenic diet.Two siblings (girl and boy), 7- and 5-year-old, both affected with GSD IIIa, developed severe and rapidly worsening left ventricular hypertrophy in the first years of life, while treated with frequent diurnal and nocturnal hyperproteic meals followed by orally administered uncooked cornstarch. Subsequently they were treated with high-fat (60%) and high-protein (25%), low-carbohydrate (15%) diet. After 12 months exertion dyspnea disappeared in the girl and biochemical blood tests, cardiac enzymes, and congestive heart failure markers improved in both (CK 3439→324, 1304→581 U/L; NT-proBNP 2084→206, 782→135 pg/mL, respectively); ultrasound assessment in both patients showed a relevant reduction of the thickness of interventricular septum (30→16, 16→11 mm, respectively) and left ventricle posterior wall (18→7, 13→8 mm, respectively) and an improvement of the outflow obstruction. A diet rich in fats as well as proteins and poor in carbohydrates could be a beneficial therapeutic choice for GSD III with cardiomyopathy. Future research is needed to confirm the beneficial effect of this treatment and to design treatment strategies with the aim to provide alternative source of energy and prevent glycogen accumulation.

  12. Altered spatiotemporal expression of collagen types I, III, IV, and VI in Lpar3-deficient peri-implantation mouse uterus.

    Science.gov (United States)

    Diao, Honglu; Aplin, John D; Xiao, Shuo; Chun, Jerold; Li, Zuguo; Chen, Shiyou; Ye, Xiaoqin

    2011-02-01

    Lpar3 is upregulated in the preimplantation uterus, and deletion of Lpar3 leads to delayed uterine receptivity in mice. Microarray analysis revealed that there was higher expression of Col3a1 and Col6a3 in the Preimplantation Day 3.5 Lpar3(-/-) uterus compared to Day 3.5 wild-type (WT) uterus. Since extracellular matrix (ECM) remodeling is indispensable during embryo implantation, and dynamic spatiotemporal alteration of specific collagen types is part of this process, this study aimed to characterize the expression of four main uterine collagen types: fibril-forming collagen (COL) I and COL III, basement membrane COL IV, and microfibrillar COL VI in the peri-implantation WT and Lpar3(-/-) uterus. An observed delay of COL III and COL VI clearance in the Lpar3(-/-) uterus may be associated with higher preimplantation expression of Col3a1 and Col6a3. There was also delayed clearance of COL I and delayed deposition of COL IV in the decidual zone in the Lpar3(-/-) uterus. These changes were different from the effects of 17beta-estradiol and progesterone on uterine collagen expression in ovariectomized WT uterus, indicating that the altered collagen expression in Lpar3(-/-) uterus is unlikely to be a result of alterations in ovarian hormones. Decreased expression of several genes encoding matrix-degrading metallo- and serine proteinases was observed in the Lpar3(-/-) uterus. These results demonstrate that pathways downstream of LPA3 are involved in the dynamic remodeling of ECM in the peri-implantation uterus.

  13. Chicken line-dependent mortality after experimental infection with three type IIxIII recombinant Toxoplasma gondii clones.

    Science.gov (United States)

    Schares, G; Herrmann, D C; Maksimov, P; Matzkeit, B; Conraths, F J; Moré, G; Preisinger, R; Weigend, S

    2017-09-01

    Three genetically different clones of Toxoplasma gondii, also different in mouse virulence, were studied by experimental infection in chickens. For the experiments, four chicken lines were used, which differed in phylogenetic origin and performance level: two white egg layer lines, one with high laying performance (WLA), one with low (R11) and two brown layer lines, also displaying high (BLA) and low (L68) egg number. Chickens were intraperitoneally infected with three different T. gondii isolates representing type IIxIII recombinant clones, i.e. showing both, type II- and type III-specific alleles. These clones (K119/2 2C10, B136/1 B6H6, K119/2 A7) had exhibited virulence differences in a mouse model. In chickens, a significantly higher mortality was observed in white layer lines, but not in brown layer lines, suggesting that differences in the phylogenetic background may influence the susceptibility of chickens for toxoplasmosis. In addition, antibody (IgY) levels varied in surviving chickens at 31 days post infection. While low to intermediate antibody levels were observed in white layers, intermediate to high levels were measured in brown layers. Infection with a T. gondii clone showing low chicken virulence resulted in higher antibody levels in all chicken lines compared to infection with T. gondii clones of intermediate or high chicken virulence. This was in agreement with the parasite load as determined by real-time PCR. Overall, results show that progeny resulting from natural sexual recombination of T. gondii clonal lineages, may differ in their virulence for mice and chickens. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice.

    Science.gov (United States)

    Asp, Linnéa; Beraki, Simret; Kristensson, Krister; Ogren, Sven Ove; Karlsson, Håkan

    2009-08-01

    Epidemiological studies suggest that early life infections may contribute to the development of psychiatric disorders characterized by cognitive deficits. Here, we studied the effects of a neonatal influenza A/WSN/33 virus infection on locomotor activity, working memory and emotional behavior in adult mice. In addition to wild type mice, immunodeficient (Tap1(-/-)) mice lacking functional CD8(+) T cells, were included in the study to model the potential influence of a genetic deficit relating to virus clearance. Three to four months after the infection, infected Tap1(-/-) mice, but not wild type mice, exhibited deficits in working memory as well as increased rearing activity and anxiety. In the medial prefrontal cortices of these infected Tap1(-/-) mice reduced levels of type III Nrg1 transcripts were observed supporting a role for neuregulin 1 signaling in neuronal circuits involved in working memory. Virus replication, distribution or clearance did not differ between the two genotypes. The lack of CD8(+) T cells, however, appeared to contribute to a more pronounced glia response in Tap1(-/-) than in wild type mice. Thus, the present study suggest that the risk of developing deficits in cognitive and emotional behavior following a CNS infection during brain development is influenced by genetic variation in genes involved in the immune response.

  15. [COMPARISON OF EFFECTIVENESS BETWEEN TWO OPERATIVE TECHNIQUES OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION FOR TREATMENT OF Tossy TYPE III ACROMIOCLAVICULAR JOINT DISLOCATION].

    Science.gov (United States)

    Tang, Hongwei; Gao, Sheng; Yin, Yong; Li, Yunfei; Han, Qingtian; Li, Huizhang

    2015-11-01

    To evaluate and compare the effectiveness of double Endobutton technique and suture anchor combined Endobutton plate in the treatment of Tossy type III acromioclavicular joint dislocation. Between May 2010 and March 2014, a retrospective study was preformed on 56 patients with Tossy type III acromioclavicular joint dislocation. The coracoclavicular ligament was reconstructed with double Endobutton technique in 31 cases (Endobutton group), and with suture anchor combined Endobutton plate in 25 cases (Anchor group). There was no significant difference in age, gender, injury causes, injury side, associated injury, medical comorbidities, and disease duration between 2 groups (P>0.05). The operation time, medical device expenses, postoperative complications, preoperative and postoperative Constant-Murley scores, and postoperative Karlsson grading of the injured shoulder were compared between 2 groups. The average operation time in Endobutton group was significantly greater than that in Anchor group (t = 4.285, P = 0.000); there was no significant difference in the medical device expenses between 2 groups (t = 1.555, P = 0.126). Primary healing of incision was obtained in all patients of 2 groups; no early complications of infection and skin necrosis occurred. All patients were followed up 15.6 months on average (range, 11-35 months). During follow-up, some loss of reduction and ectopic ossification in the coracoclavicular gap were observed in 1 case and 6 cases of Endobutton group, respectively. No recurrence of acromioclavicular joint dislocation, implant fixation loosening and broken, and secondary fractures occurred in the other patients. There was significant difference in the incidence of postoperative complications between 2 groups (P = 0.013). Constant-Murley scores of the injured shoulder significantly increased at 9 months after operation when compared with preoperative values in 2 groups (P 0.05). At last follow-up, there was no significant difference in

  16. On the molecular basis of D-bifunctional protein deficiency type III.

    Directory of Open Access Journals (Sweden)

    Maija L Mehtälä

    Full Text Available Molecular basis of D-bifunctional protein (D-BP deficiency was studied with wild type and five disease-causing variants of 3R-hydroxyacyl-CoA dehydrogenase fragment of the human MFE-2 (multifunctional enzyme type 2 protein. Complementation analysis in vivo in yeast and in vitro enzyme kinetic and stability determinants as well as in silico stability and structural fluctuation calculations were correlated with clinical data of known patients. Despite variations not affecting the catalytic residues, enzyme kinetic performance (K(m, V(max and k(cat of the recombinant protein variants were compromised to a varying extent and this can be judged as the direct molecular cause for D-BP deficiency. Protein stability plays an additional role in producing non-functionality of MFE-2 in case structural variations affect cofactor or substrate binding sites. Structure-function considerations of the variant proteins matched well with the available data of the patients.

  17. Type III frontal sinusotomy: surgical technique, indications, outcomes, a multi-university retrospective study of 120 cases.

    Science.gov (United States)

    Eloy, P; Vlaminck, S; Jorissen, M; Hellings, P; Timmermans, M; Daele, J; Ransky, P; Hassid, S; Van Zele, T; Bachert, C; Poirrier, A L; Bertrand, B

    2011-01-01

    Draf in 1991. The procedure--which is also known as the modified endoscopic Lothrop procedure--aims to create the largest possible anteroposterior and lateral to lateral opening between both frontal sinuses and the nasal cavities. This requires the resection of the medial floor of both frontal sinuses, the intersinus septum and the superior nasal septum. The authors present a retrospective study including a cohort of 120 patients who underwent surgery in six Belgian university ENT departments. Mean follow-up was 24.6 months (range: 5-36 months). This paper describes the surgical procedure and reviews the indications, comorbidities, outcomes and complications of the type III frontal sinusotomy. Some correlations are also established with the data published in the worldwide literature. The authors conclude that the Draf III is a demanding procedure requiring considerable expertise in endoscopic sinus surgery. The procedure is effective with a success rate of 87.5%. Indeed, 12.5% of patients only experienced closure of the neoostium while 20% of all the patients had unchanged or worse symptomatology. The percentage of post-operative complications is 7.5%. All complications were managed successfully.

  18. Reemergence of dengue virus type-3 (subtype-III in India: Implications for increased incidence of DHF & DSS

    Directory of Open Access Journals (Sweden)

    Tewari KN

    2006-07-01

    Full Text Available Abstract Background Dengue virus infection has recently taken endemic proportion in India implicating all the four known dengue serotypes. There was a major dengue outbreak in northern India including Delhi in October- December, 2003 and again in 2004. We have carried out a detailed investigation of the 2004 outbreak by Serosurveillance, RT-PCR, nested PCR, virus isolation and genotyping. We also report the molecular epidemiological investigation of these outbreaks. Results The serological investigation of 162 suspected serum samples using an in-house dengue dipstick ELISA revealed 11%-IgM, 51%-IgG and 38%-both IgM and IgG antibody positivity. The RT-PCR analysis revealed presence of dengue RNA in 17 samples. Further subtyping and genotyping by nested PCR and nucleotide sequencing of C-prM gene junction revealed the association of subtype III of dengue virus type 3 in the outbreak. Conclusion The sudden shifting and dominance of the dengue virus serotype-3 (subtype III replacing the earlier circulating serotype-2 (subtype IV is a point of major concern and may be attributed to increased incidence of DHF and DSS in India.

  19. Content and technical evaluation of Type III Iranian medical universities\\' websites

    Directory of Open Access Journals (Sweden)

    Khadejeh Shabankareh

    2016-05-01

    Full Text Available Background: Besides the role that universities websites have in reflection of universities’ educational and research activities, they have also significant importance in promotion of universities’ national and international ranking in webometrics ranking of world universities and also in webometric ranking of Islamic world Science Citation and subsequently obtaining national and international credibility and gaining student and funding. So, continuous evaluation of universities websites in different aspects, especially based on considering index of these ranking systems, is important. Therefore, present study aimed to review the situation of Type 3 Iranian medical universities’ websites based on content and technical features effecting on promotion of webometric rank. Materials and Methods : Present study is a survey with descriptive approach which descriptive the present situation of Type 3 Iranian medical universities’ websites. Data were collected using a researcher-made checklist which was consisted of two parts including content criteria effecting on webometric ranking (50 criteria and technical criteria of search engines optimization (52 criteria. Content evaluation of websites was done by researcher direct referring and observing. In order to evaluation of these websites, based on technical criteria of search engines optimization, automatic tools about website evaluation were used. Data were analyzed by SPSS20. Results: The finding of this study showed that, Gonabad, Bushehr & Shahrekord universities of medical sciences have the most accommodation with the research checklist.  Bam, Dezful & Jiroft universities of medical sciences have the least accommodation. According to research findings less than 50 percent of the research community, reached more than 50 percent of the criteria in checklist. Conclusion: Evaluation of studied websites indicated that whole websites are far from ideal situation. So type 3 medical universities

  20. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt;

    2015-01-01

    OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic...... myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance...

  1. Travelling wave solutions for higher-order wave equations of kdv type (iii).

    Science.gov (United States)

    Li, Jibin; Rui, Weigou; Long, Yao; He, Bin

    2006-01-01

    By using the theory of planar dynamical systems to the travelling wave equation of a higher order nonlinear wave equations of KdV type, the existence of smooth solitary wave, kink wave and anti-kink wave solutions and uncountably infinite many smooth and non-smooth periodic wave solutions are proved. In different regions of the parametric space, the sufficient conditions to guarantee the existence of the above solutions are given. In some conditions, exact explicit parametric representations of these waves are obtain.

  2. STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III.

    Science.gov (United States)

    Avery, O T; Macleod, C M; McCarty, M

    1944-02-01

    1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered. 2. Methods for the isolation and purification of the active transforming material are described. 3. The data obtained by chemical, enzymatic, and serological analyses together with the results of preliminary studies by electrophoresis, ultracentrifugation, and ultraviolet spectroscopy indicate that, within the limits of the methods, the active fraction contains no demonstrable protein, unbound lipid, or serologically reactive polysaccharide and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid. 4. Evidence is presented that the chemically induced alterations in cellular structure and function are predictable, type-specific, and transmissible in series. The various hypotheses that have been advanced concerning the nature of these changes are reviewed.

  3. Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma

    Directory of Open Access Journals (Sweden)

    Jie Tang

    2014-04-01

    Full Text Available We investigated the prostate elasticity displayed by elastography and its correlation with the content and distribution of collagen type I (Col1 and type III (Col3. A total of 62 patients underwent transrectal real-time tissue elastography (TRTE examinations. Targeted biopsies were performed after 12-core systematic biopsy. The tissues corresponding to the elastograms were stained with picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and the collagen volume fraction (CVF of these two types of collagen fibers was calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 ± 0.02 and 0.02 ± 0.01 (P = 0.002, respectively. The CVFs of Col3 in the stiff and soft groups were 0.05 ± 0.04 and 0.07 ± 0.03 (P = 0.13, respectively. The circular analysis results showed that collagen fibers were disorganized both in the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some parallelization was observed in the sections. The distributions of Col1 and Col3 were different between the stiff and soft groups (P = 0.03. In conclusion, the texture of the prostate is due to the content of Col1 and its relative correlation with Col3.

  4. An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference

    DEFF Research Database (Denmark)

    Peng, Wenfang; Feng, Mingxia; Feng, Xu;

    2015-01-01

    CRISPR-Cas systems provide a small RNA-based mechanism to defend against invasive genetic elements in archaea and bacteria. To investigate the in vivo mechanism of RNA interference by two type III-B systems (Cmr-α and Cmr-β) in Sulfolobus islandicus, a genetic assay was developed using plasmids...... carrying an artificial mini-CRISPR (AC) locus with a single spacer. After pAC plasmids were introduced into different strains, Northern analyses confirmed that mature crRNAs were produced from the plasmid-borne CRISPR loci, which then guided gene silencing to target gene expression. Spacer mutagenesis....... islandicus Cmr-α mediated transcription-dependent DNA interference, the Cmr-α constitutes the first CRISPR system exhibiting dual targeting of RNA and DNA....

  5. Physeal fractures of the distal tibia and fibula (Salter-Harris Type I, II, III, and IV fractures).

    Science.gov (United States)

    Podeszwa, David A; Mubarak, Scott J

    2012-06-01

    Physeal fractures of the distal tibia and fibula are common and can be seen at any age, although most are seen in the adolescent. An understanding of the unique anatomy of the skeletally immature ankle in relation to the mechanism of injury will help one understand the injury patterns seen in this population. A thorough clinical exam is critical to the diagnosis and treatment of these injuries and the avoidance of potentially catastrophic complications. Nondisplaced physeal fractures of the distal tibia and fibula can be safely treated nonoperatively. Displaced fractures should undergo a gentle reduction with appropriate anesthesia while multiple reduction attempts should be avoided. Gapping of the physis >3 mm after reduction should raise the suspicion of entrapped periosteum that will increase the risk of premature physeal closure. Open reduction of displaced Salter-Harris type III and IV fractures is critical to maintain joint congruity and minimize the risk of physeal arrest.

  6. An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference

    DEFF Research Database (Denmark)

    Peng, Wenfang; Feng, Mingxia; Feng, Xu

    2015-01-01

    CRISPR-Cas systems provide a small RNA-based mechanism to defend against invasive genetic elements in archaea and bacteria. To investigate the in vivo mechanism of RNA interference by two type III-B systems (Cmr-α and Cmr-β) in Sulfolobus islandicus, a genetic assay was developed using plasmids...... carrying an artificial mini-CRISPR (AC) locus with a single spacer. After pAC plasmids were introduced into different strains, Northern analyses confirmed that mature crRNAs were produced from the plasmid-borne CRISPR loci, which then guided gene silencing to target gene expression. Spacer mutagenesis....... islandicus Cmr-α mediated transcription-dependent DNA interference, the Cmr-α constitutes the first CRISPR system exhibiting dual targeting of RNA and DNA....

  7. Utilizing avidity to improve antifreeze protein activity: a type III antifreeze protein trimer exhibits increased thermal hysteresis activity.

    Science.gov (United States)

    Can, Özge; Holland, Nolan B

    2013-12-03

    Antifreeze proteins (AFPs) are ice growth inhibitors that allow the survival of several species living at temperatures colder than the freezing point of their bodily fluids. AFP activity is commonly defined in terms of thermal hysteresis, which is the difference observed for the solution freezing and melting temperatures. Increasing the thermal hysteresis activity of these proteins, particularly at low concentrations, is of great interest because of their wide range of potential applications. In this study, we have designed and expressed one-, two-, and three-domain antifreeze proteins to improve thermal hysteresis activity through increased binding avidity. The three-domain type III AFP yielded significantly greater activity than the one- and two-domain proteins, reaching a thermal hysteresis of >1.6 °C at a concentration of hysteresis activity.

  8. Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Hiroyuki [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan); Kondo, Shin [ZOEGENE Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Tsuyoshi; Noguchi, Hiroshi [School of Pharmaceutical Sciences and the COE21 Program, University of Shizuoka, Shizuoka 422-8526 (Japan); Sugio, Shigetoshi, E-mail: ssugio@rc.m-kagaku.co.jp [ZOEGENE Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Ikuro, E-mail: ssugio@rc.m-kagaku.co.jp [School of Pharmaceutical Sciences and the COE21 Program, University of Shizuoka, Shizuoka 422-8526 (Japan); PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kohno, Toshiyuki, E-mail: ssugio@rc.m-kagaku.co.jp [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan)

    2006-09-01

    Pentaketide chromone synthase from A. arborescens has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 1.6 Å. Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase that catalyzes the formation of 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group P2{sub 1}, with unit-cell parameters a = 73.2, b = 88.4, c = 70.0 Å, α = γ = 90.0, β = 95.6°. Diffraction data were collected to 1.6 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  9. Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone

    Science.gov (United States)

    Morita, Hiroyuki; Kondo, Shin; Abe, Tsuyoshi; Noguchi, Hiroshi; Sugio, Shigetoshi; Abe, Ikuro; Kohno, Toshiyuki

    2006-01-01

    Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase that catalyzes the formation of 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group P21, with unit-cell parameters a = 73.2, b = 88.4, c = 70.0 Å, α = γ = 90.0, β = 95.6°. Diffraction data were collected to 1.6 Å resolution using synchrotron radiation at BL24XU of SPring-8. PMID:16946474

  10. Search for heavy lepton partners of neutrinos in the context of type-III Seesaw Mechanism at CMS

    CERN Document Server

    AUTHOR|(CDS)2091444

    2015-01-01

    The Seesaw Mechanism was introduced to explain why the masses of neutrinos are many orders of magnitude smaller than the other lepton masses. Considering neutrinos as Majorana particles, ``natural'' Yukawa couplings yield neutrinos with very small masses, along with heavy partners. Such particles may be observable at the LHC experiments. CMS searched for a fermionic triplet (type-III Seesaw Mechanism) by selecting events with three isolated leptons, jets and missing transverse energy in the final state. Backgrounds are due to events with leptons from electroweak processes either leptons coming from secondary vertices or ``fake leptons''. The estimate of fake leptons is a crucial point of the analysis. Results obtained with data collected in 2012, corresponding to 19.7~$\\mbox{fb}^{-1}$ and $\\sqrt{s}$= 8 TeV, show no evidence of signal, and so we have set lower limits on the masses of the fermionic triplet.

  11. A derivation of Holling's type I, II and III functional responses in predator-prey systems.

    Science.gov (United States)

    Dawes, J H P; Souza, M O

    2013-06-21

    Predator-prey dynamics is most simply and commonly described by Lotka-Volterra-type ordinary differential equations (ODEs) for continuous population density variables in the limit of large population sizes. One popular extension of these ODEs is the so-called Rosenzweig-MacArthur model in which various interaction rates between the populations have a nonlinear dependence on the prey concentration. Nonlinear 'functional responses' of this type were originally proposed by Holling on the basis of a general argument concerning the allocation of a predator's time between two activities: 'prey searching' and 'prey handling'. Although these functional responses are constructed in terms of the behaviour of an individual predator, they are routinely incorporated at the population level in models that include reproduction and death. In this paper we derive a novel three variable model for the simplest possible mathematical formulation of predator-prey dynamics that allows the interplay between these various processes to take place, on their different characteristic timescales. We study its properties in detail and show how it reduces to Holling's functional responses in special limits. As a result we are able to establish direct links between individual-level and population-level behaviour in the context of these well-known functional responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Treatment of Gartland type III pediatric supracondylar humerus fractures with the Kapandji technique in the prone position.

    Science.gov (United States)

    Kao, Hsuan-Kai; Yang, Wen-E; Li, Wei-Chun; Chang, Chia-Hsieh

    2014-06-01

    The purpose of this study was to report the efficacy of the Kapandji technique performed in the prone position for humeral supracondylar fractures in children. Retrospective. Level I trauma center. We retrospectively reviewed 34 children with Gartland type III supracondylar humerus fractures. There were 22 boys and 12 girls with a mean age of 5.2 years (range, 1-12.7 years). Closed reduction and the Kapandji technique were performed in the prone position for all patients. The mean follow-up was 17.4 months (range, 13.2-24.8 months). We assessed preoperative and postoperative radiographs to evaluate the quality of the reduction. The clinical outcome was assessed according to the criteria of Flynn. All operations were performed in a closed manner, no cases required open reduction. Loss of reduction after K-wire fixation was identified in 2 patients. There were no pin-related nerve injuries. The mean range of elbow motion was 139.6 degrees. The clinical outcome was excellent in 31 patients, good in 2 patients (97% excellent or good), and fair in 1 patient. This technique is an effective and safe option to treat type III supracondylar humerus fractures in children. In patients with severe soft tissue swelling, unstable fracture reduction, or unable to achieve acceptable reduction, this technique could facilitate fracture reduction and avoid unnecessary open reduction. The disadvantage of this technique is that the prone position is less desirable for airway management. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  13. The Structures of Coiled-Coil Domains from Type III Secretion System Translocators Reveal Homology to Pore-Forming Toxins

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Dickenson, Nicholas E.; Patil, Mrinalini; Keightley, Andrew; Wyckoff, Gerald J.; Picking, William D.; Picking, Wendy L.; Geisbrecht, Brian V. (UMKC); (OKLU)

    2012-03-26

    Many pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore-forming translocators, IpaB and IpaC. While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease-stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 {angstrom} and 2.8 {angstrom} limiting resolution, respectively. These newly identified domains are composed of extended-length (114 {angstrom} in IpaB and 71 {angstrom} in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events.

  14. Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins

    Energy Technology Data Exchange (ETDEWEB)

    Meshcheryakov, Vladimir A. [Okinawa Instiute of Science and Technology, Okinawa 904-0495 (Japan); Kitao, Akio [University of Tokyo, Tokyo 113-0032 (Japan); Core Research for Evolutionary Science and Technology, Tokyo 113-0032 (Japan); Matsunami, Hideyuki; Samatey, Fadel A., E-mail: f.a.samatey@oist.jp [Okinawa Instiute of Science and Technology, Okinawa 904-0495 (Japan)

    2013-05-01

    Crystal structures of the cytoplasmic domain of FlhB from S. typhimurium and A. aeolicus were solved at 2.45 and 2.55 Å resolution, respectively. The deletion of a short loop in the cytoplasmic domain of Salmonella FlhB completely abolishes secretion by the type III secretion system. A molecular-dynamics simulation shows that the deletion of the loop affects the flexibility of a linker between the transmembrane and cytoplasmic domains of FlhB. The membrane protein FlhB is a highly conserved component of the flagellar secretion system. It is composed of an N-terminal transmembrane domain and a C-terminal cytoplasmic domain (FlhB{sub C}). Here, the crystal structures of FlhB{sub C} from Salmonella typhimurium and Aquifex aeolicus are described at 2.45 and 2.55 Å resolution, respectively. These flagellar FlhB{sub C} structures are similar to those of paralogues from the needle type III secretion system, with the major difference being in a linker that connects the transmembrane and cytoplasmic domains of FlhB. It was found that deletion of a short flexible loop in a globular part of Salmonella FlhB{sub C} leads to complete inhibition of secretion by the flagellar secretion system. Molecular-dynamics calculations demonstrate that the linker region is the most flexible part of FlhB{sub C} and that the deletion of the loop reduces this flexibility. These results are in good agreement with previous studies showing the importance of the linker in the function of FlhB and provide new insight into the relationship between the different parts of the FlhB{sub C} molecule.

  15. Functional interaction between type III-secreted protein IncA of Chlamydophila psittaci and human G3BP1.

    Science.gov (United States)

    Borth, Nicole; Litsche, Katrin; Franke, Claudia; Sachse, Konrad; Saluz, Hans Peter; Hänel, Frank

    2011-01-31

    Chlamydophila (Cp.) psittaci, the causative agent of psittacosis in birds and humans, is the most important zoonotic pathogen of the family Chlamydiaceae. These obligate intracellular bacteria are distinguished by a unique biphasic developmental cycle, which includes proliferation in a membrane-bound compartment termed inclusion. All Chlamydiaceae spp. possess a coding capacity for core components of a Type III secretion apparatus, which mediates specific delivery of anti-host effector proteins either into the chlamydial inclusion membrane or into the cytoplasm of target eukaryotic cells. Here we describe the interaction between Type III-secreted protein IncA of Cp. psittaci and host protein G3BP1 in a yeast two-hybrid system. In GST-pull down and co-immunoprecipitation experiments both in vitro and in vivo interaction between full-length IncA and G3BP1 were shown. Using fluorescence microscopy, the localization of G3BP1 near the inclusion membrane of Cp. psittaci-infected Hep-2 cells was demonstrated. Notably, infection of Hep-2 cells with Cp. psittaci and overexpression of IncA in HEK293 cells led to a decrease in c-Myc protein concentration. This effect could be ascribed to the interaction between IncA and G3BP1 since overexpression of an IncA mutant construct disabled to interact with G3BP1 failed to reduce c-Myc concentration. We hypothesize that lowering the host cell c-Myc protein concentration may be part of a strategy employed by Cp. psittaci to avoid apoptosis and scale down host cell proliferation.

  16. Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system

    Directory of Open Access Journals (Sweden)

    Singsuksawat Ekapot

    2010-06-01

    Full Text Available Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis. Results Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS. Microarray data were verified by reverse transcriptase-polymerase chain reactions (RT-PCR. Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system. Conclusions B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei.

  17. Scapular dyskinesis and SICK syndrome in patients with a chronic type III acromioclavicular dislocation. Results of rehabilitation.

    Science.gov (United States)

    Carbone, Stefano; Postacchini, Roberto; Gumina, Stefano

    2015-05-01

    Scapular dyskinesis has been related to acromioclavicular injuries. A rehabilitation protocol has been studied in order to treat scapular dyskinesis, but it has not yet been evaluated. This rehabilitation programme was adopted to improve the shoulder function, thereby improving the scapular dyskinesis in patients with chronic acromioclavicular dislocation. Twenty-four patients diagnosed with chronic type III acromioclavicular dislocation and scapular dyskinesis that have already been conservatively treated were enrolled in the rehabilitation protocol and analysed. Fourteen of these patients had a Scapular Inferior Coracoid dysKinesis (SICK) Syndrome. The adopted rehabilitation protocol consisted of 12 strengthening and stretching exercises of the scapulae. The final follow-ups were performed after 6 weeks, 6 months and 12 months using clinical measurements of scapular position and clinical evaluation of the scapular motion. In order to evaluate the SICK scapula syndrome, we used the SICK Scapula Rating Scale. The shoulder function was evaluated with a Constant Score and a Subjective Shoulder Value. After 12 months, the follow-up concluded that the scapular dyskinesis was no longer present in 18/23 patients (78.2 %). SICK scapula syndrome was observed in 4/8 patients with a scapular malposition. The Scapula Rating Scale score in 4 patients with SICK scapula was 7.5 points. After 12 months of rehabilitation, the mean Constant Score and Subjective Shoulder Value grew up to 85 points. The scapular dyskinesis and SICK syndrome secondary to chronic type III AC dislocation can be treated with the proposed rehabilitation protocol resulting in positive improvements of the shoulder function within 6 weeks; however, patients that do not respond to the rehabilitation programme will not improve with extended rehabilitation time. It is important to advise patients of the specific exercises for the prevention/treatment of scapular dyskinesis in the rehabilitation programme after

  18. Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.

    Directory of Open Access Journals (Sweden)

    Wieslaw Swietnicki

    Full Text Available Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC(50 values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.

  19. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, Christina;

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN...... had a more modest antiviral activity. Finally, pretreatment with IFN-lambda enhanced the levels of IFN-gamma in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between...

  20. Lambda Interferon (IFN-gamma), a Type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, C.;

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN...... had a more modest antiviral activity. Finally, pretreatment with IFN-lambda enhanced the levels of IFN-gamma in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between...